document_title: Mitochondrion

question_text: mitochondria produce atp using what kind of process

question_tokens: mitochondria produce atp using what kind of process

text: Mitochondrion

text: History

text: The first observations of intracellular structures that probably represented mitochondria were published in the 1840s.[19] Richard Altmann, in 1890, established them as cell organelles and called them "bioblasts".[19][20] The term "mitochondria" was coined by Carl Benda in 1898.[19][21] Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. In 1904, Friedrich Meves, made the first recorded observation of mitochondria in plants in cells of the white waterlily, Nymphaea alba[19][22] and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but almost exclusively based on morphological observations.[19] In 1913, particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had also postulated a similar particle mechanism, disagreed on the chemical nature of the respiration. It was not until 1925, when David Keilin discovered cytochromes, that the respiratory chain was described.[19]

text: In 1939, experiments using minced muscle cells demonstrated that cellular respiration using one oxygen atom can form two adenosine triphosphate (ATP) molecules, and, in 1941, the concept of the phosphate bonds of ATP being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann. In the following years, the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known.[19] The introduction of tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946, he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitchondria. Eugene Kennedy and Albert Lehninger discovered in 1948 that mitochondria are the site of oxidative phosphorylation in eukaryotes. Over time, the fractionation method was further developed, improving the quality of the mitochondria isolated, and other elements of cell respiration were determined to occur in the mitochondria.[19]

text: The first high-resolution electron micrographs appeared in 1952, replacing the Janus Green stains as the preferred way of visualising the mitochondria.[19] This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane. It also showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell.

text: The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957.[23]

text: In 1967, it was discovered that mitochondria contained ribosomes.[24] In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA being completed in 1976.[19]

text: Origin and evolution

text: There are two hypotheses about the origin of mitochondria: endosymbiotic and autogenous. The endosymbiotic hypothesis suggests that mitochondria were originally prokaryotic cells, capable of implementing oxidative mechanisms that were not possible for eukaryotic cells; they became endosymbionts living inside the eukaryote.[25] In the autogenous hypothesis, mitochondria were born by splitting off a portion of DNA from the nucleus of the eukaryotic cell at the time of divergence with the prokaryotes; this DNA portion would have been enclosed by membranes, which could not be crossed by proteins. Since mitochondria have many features in common with bacteria, the endosymbiotic hypothesis is more widely accepted.[25][26]

text: A mitochondrion contains DNA, which is organized as several copies of a single, usually circular, chromosome. This mitochondrial chromosome contains genes for redox proteins, such as those of the respiratory chain. The CoRR hypothesis proposes that this co-location is required for redox regulation. The mitochondrial genome codes for some RNAs of ribosomes, and the 22 tRNAs necessary for the translation of messenger RNAs into protein. The circular structure is also found in prokaryotes. The proto-mitochondrion was probably closely related to the Rickettsia.[27][28] However, the exact relationship of the ancestor of mitochondria to the alphaproteobacteria and whether the mitochondrion was formed at the same time or after the nucleus, remains controversial.[29]

text: A recent study[30] by researchers of the University of Hawaii at Manoa and the Oregon State University indicates that the SAR11 clade of bacteria shares a relatively recent common ancestor with the mitochondria existing in most eukaryotic cells.

text:
Schematic phylogeny of Alphaproteobacteria, according to Ferla et al. (2013) [31]

Magnetococcidae

Magnetococcales

Magnetococcaceae

Magnetococcus marinus

Caulobacteridae

Rhodospirillales, Sphingomonadales, Rhodobacteraceae, Rhizobiales, etc.

Holosporales

Rickettsidae

Pelagibacterales

Pelagibacteraceae

Pelagibacter

subgroups Ib, II, IIIa, IIIb, IV and V

Proto-mitochondria

Anaplasmataceae

Ehrlichia

Anaplasma

Wolbachia

Neorickettsia

Midichloriaceae

Midichloria

Rickettsiaceae

Rickettsia

Robust 16S + 23S phylogeny of Rickettsidae from Ferla et al. [31]

text: The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure.[32] They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes, which are coded for by nuclear DNA.

text: The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis.[33] The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. This symbiotic relationship probably developed 1.7[34] to 2[35] billion years ago.

text: A few groups of unicellular eukaryotes have only vestigial mitochondria or derived structures: the microsporidians, metamonads, and archamoebae.[36] These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, which once suggested that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attraction—they are derived groups and retain genes or organelles derived from mitochondria (e.g., mitosomes and hydrogenosomes).[1]

text: Monocercomonoides appear to have lost their mitochondria completely and at least some of the mitochondrial functions seem to be carried out by cytoplasmic proteins now.[37]

text: Structure

text: A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins.[13] The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion. They are:

text:
the outer mitochondrial membrane,
the intermembrane space (the space between the outer and inner membranes),
the inner mitochondrial membrane,
the cristae space (formed by infoldings of the inner membrane), and
the matrix (space within the inner membrane).

tag: ol

text: Mitochondria stripped of their outer membrane are called mitoplasts.

text: Outer membrane

text: The outer mitochondrial membrane, which encloses the entire organelle, is 60 to 75 angstroms (Å) thick. It has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral membrane proteins called porins. These porins form channels that allow molecules of 5000 daltons or less in molecular weight to freely diffuse from one side of the membrane to the other.[13] Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane.[39] Mitochondrial pro-proteins are imported through specialised translocation complexes. The outer membrane also contains enzymes involved in such diverse activities as the elongation of fatty acids, oxidation of epinephrine, and the degradation of tryptophan. These enzymes include monoamine oxidase, rotenone-insensitive NADH-cytochrome c-reductase, kynurenine hydroxylase and fatty acid Co-A ligase. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death.[40] The mitochondrial outer membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria. [41] Outside the outer membrane there are small (diameter: 60Å) particles named sub-units of Parson.

text: Intermembrane space

text: The intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in the cytosol.[13] However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c.[40]

text: Inner membrane

text: The inner mitochondrial membrane contains proteins with five types of functions:[13]

text:
Those that perform the redox reactions of oxidative phosphorylation
ATP synthase, which generates ATP in the matrix
Specific transport proteins that regulate metabolite passage into and out of the matrix
Protein import machinery
Mitochondrial fusion and fission protein

text: It contains more than 151 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion.[13] In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes.[42] Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable.[13] Unlike the outer membrane, the inner membrane doesn't contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1.[39] In addition, there is a membrane potential across the inner membrane, formed by the action of the enzymes of the electron transport chain.

text: Cristae

text: The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times as large as the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. These folds are studded with small round bodies known as F1 particles or oxysomes. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function.[43]

text: One recent mathematical modeling study has suggested that the optical properties of the cristae in filamentous mitochondria may affect the generation and propagation of light within the tissue.[44]

text: Matrix

text: The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion.[13] The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.[13]

text: Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 genes: 22 tRNA, 2 rRNA, and 13 peptide genes.[45] The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.

text: Mitochondria-associated ER membrane (MAM)

text: The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis. Once considered a technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAM—the interface between mitochondria and the ER.[46] Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy.[46] Such studies estimate that at the MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10–25 nm and held together by protein tethering complexes.[46][47][48]

text: Purified MAM from subcellular fractionation has been shown to be enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca2+ signaling.[46][48] These hints of a prominent role for the MAM in the regulation of cellular lipid stores and signal transduction have been borne out, with significant implications for mitochondrial-associated cellular phenomena, as discussed below. Not only has the MAM provided insight into the mechanistic basis underlying such physiological processes as intrinsic apoptosis and the propagation of calcium signaling, but it also favors a more refined view of the mitochondria. Though often seen as static, isolated 'powerhouses' hijacked for cellular metabolism through an ancient endosymbiotic event, the evolution of the MAM underscores the extent to which mitochondria have been integrated into overall cellular physiology, with intimate physical and functional coupling to the endomembrane system.

text: Phospholipid transfer

text: The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face.[49][50] Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity.[51][52] But mitochondria are not only a destination for the phospholipids they finish synthesis of; rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism.[50][52]

text: Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles.[49] In contrast to the standard vesicular mechanism of lipid transfer, evidence indicates that the physical proximity of the ER and mitochondrial membranes at the MAM allows for lipid flipping between opposed bilayers.[52] Despite this unusual and seemingly energetically unfavorable mechanism, such transport does not require ATP.[52] Instead, in yeast, it has been shown to be dependent on a multiprotein tethering structure termed the ER-mitochondria encounter structure, or ERMES, although it remains unclear whether this structure directly mediates lipid transfer or is required to keep the membranes in sufficiently close proximity to lower the energy barrier for lipid flipping.[52][53]

text: The MAM may also be part of the secretory pathway, in addition to its role in intracellular lipid trafficking. In particular, the MAM appears to be an intermediate destination between the rough ER and the Golgi in the pathway that leads to very-low-density lipoprotein, or VLDL, assembly and secretion.[50][54] The MAM thus serves as a critical metabolic and trafficking hub in lipid metabolism.

text: Calcium signaling

text: A critical role for the ER in calcium signaling was acknowledged before such a role for the mitochondria was widely accepted, in part because the low affinity of Ca2+ channels localized to the outer mitochondrial membrane seemed to fly in the face of this organelle's purported responsiveness to changes in intracellular Ca2+ flux.[46][55] But the presence of the MAM resolves this apparent contradiction: the close physical association between the two organelles results in Ca2+ microdomains at contact points that facilitate efficient Ca2+ transmission from the ER to the mitochondria.[46] Transmission occurs in response to so-called "Ca2+ puffs" generated by spontaneous clustering and activation of IP3R, a canonical ER membrane Ca2+ channel.[46][47]

text: The fate of these puffs—in particular, whether they remain restricted to isolated locales or integrated into Ca2+ waves for propagation throughout the cell—is determined in large part by MAM dynamics. Although reuptake of Ca2+ by the ER (concomitant with its release) modulates the intensity of the puffs, thus insulating mitochondria to a certain degree from high Ca2+ exposure, the MAM often serves as a firewall that essentially buffers Ca2+ puffs by acting as a sink into which free ions released into the cytosol can be funneled.[46][56][57] This Ca2+ tunneling occurs through the low-affinity Ca2+ receptor VDAC1, which recently has been shown to be physically tethered to the IP3R clusters on the ER membrane and enriched at the MAM.[46][47][58] The ability of mitochondria to serve as a Ca2+ sink is a result of the electrochemical gradient generated during oxidative phosphorylation, which makes tunneling of the cation an exergonic process.[58] Normally, mild calcium influx from cytosol into the mitochondrial matrix causes transient depolarization that is corrected by pumping out protons.

text: But transmission of Ca2+ is not unidirectional; rather, it is a two-way street.[55] The properties of the Ca2+ pump SERCA and the channel IP3R present on the ER membrane facilitate feedback regulation coordinated by MAM function. In particular, the clearance of Ca2+ by the MAM allows for spatio-temporal patterning of Ca2+ signaling because Ca2+ alters IP3R activity in a biphasic manner.[46] SERCA is likewise affected by mitochondrial feedback: uptake of Ca2+ by the MAM stimulates ATP production, thus providing energy that enables SERCA to reload the ER with Ca2+ for continued Ca2+ efflux at the MAM.[56][58] Thus, the MAM is not a passive buffer for Ca2+ puffs; rather it helps modulate further Ca2+ signaling through feedback loops that affect ER dynamics.

text: Regulating ER release of Ca2+ at the MAM is especially critical because only a certain window of Ca2+ uptake sustains the mitochondria, and consequently the cell, at homeostasis. Sufficient intraorganelle Ca2+ signaling is required to stimulate metabolism by activating dehydrogenase enzymes critical to flux through the citric acid cycle.[59] However, once Ca2+ signaling in the mitochondria passes a certain threshold, it stimulates the intrinsic pathway of apoptosis in part by collapsing the mitochondrial membrane potential required for metabolism.[46] Studies examining the role of pro- and anti-apoptotic factors support this model; for example, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to reduce Ca2+ filling of the ER, leading to reduced efflux at the MAM and preventing collapse of the mitochondrial membrane potential post-apoptotic stimuli.[46] Given the need for such fine regulation of Ca2+ signaling, it is perhaps unsurprising that dysregulated mitochondrial Ca2+ has been implicated in several neurodegenerative diseases, while the catalogue of tumor suppressors includes a few that are enriched at the MAM.[58]

text: Molecular basis for tethering

text: Recent advances in the identification of the tethers between the mitochondrial and ER membranes suggest that the scaffolding function of the molecular elements involved is secondary to other, non-structural functions. In yeast, ERMES, a multiprotein complex of interacting ER- and mitochondrial-resident membrane proteins, is required for lipid transfer at the MAM and exemplifies this principle. One of its components, for example, is also a constituent of the protein complex required for insertion of transmembrane beta-barrel proteins into the lipid bilayer.[52] However, a homologue of the ERMES complex has not yet been identified in mammalian cells. Other proteins implicated in scaffolding likewise have functions independent of structural tethering at the MAM; for example, ER-resident and mitochondrial-resident mitofusins form heterocomplexes that regulate the number of inter-organelle contact sites, although mitofusins were first identified for their role in fission and fusion events between individual mitochondria.[46] Glucose-related protein 75 (grp75) is another dual-function protein. In addition to the matrix pool of grp75, a portion serves as a chaperone that physically links the mitochondrial and ER Ca2+ channels VDAC and IP3R for efficient Ca2+ transmission at the MAM.[46][47] Another potential tether is Sigma-1R, a non-opioid receptor whose stabilization of ER-resident IP3R may preserve communication at the MAM during the metabolic stress response.[60][61]

text: Perspective

text: The MAM is a critical signaling, metabolic, and trafficking hub in the cell that allows for the integration of ER and mitochondrial physiology. Coupling between these organelles is not simply structural but functional as well and critical for overall cellular physiology and homeostasis. The MAM thus offers a perspective on mitochondria that diverges from the traditional view of this organelle as a static, isolated unit appropriated for its metabolic capacity by the cell. Instead, this mitochondrial-ER interface emphasizes the integration of the mitochondria, the product of an endosymbiotic event, into diverse cellular processes.

text: Organization and distribution

text: Mitochondria (and related structures) are found in all eukaryotes (except one—the Oxymonad Monocercomonoides sp.).[2][62] Although commonly depicted as bean-like structures they form a highly dynamic network in the majority of cells where they constantly undergo fission and fusion. Mitochondria vary in number and location according to cell type. A single mitochondrion is often found in unicellular organisms. Conversely, numerous mitochondria are found in human liver cells, with about 1000–2000 mitochondria per cell, making up 1/5 of the cell volume.[13] The population of all the mitochondria of a given cell constitutes the chondriome. The mitochondrial content of otherwise similar cells can vary substantially in size and membrane potential,[63] with differences arising from sources including uneven partitioning at cell divisions, leading to extrinsic differences in ATP levels and downstream cellular processes.[64] The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum.[13] Often, they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well:[65] different structures of the mitochondrial network may afford the population a variety of physical, chemical, and signalling advantages or disadvantages.[66] Mitochondria in cells are always distributed along microtubules and the distribution of these organelles is also correlated with the endoplasmic reticulum.[67] Recent evidence suggests that vimentin, one of the components of the cytoskeleton, is also critical to the association with the cytoskeleton.[68]

text: Function

text: The most prominent roles of mitochondria are to produce the energy currency of the cell, ATP (i.e., phosphorylation of ADP), through respiration, and to regulate cellular metabolism.[14] The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs cycle. However, the mitochondrion has many other functions in addition to the production of ATP.

text: Energy conversion

text: A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose: pyruvate, and NADH, which are produced in the cytosol.[14] This type of cellular respiration known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited, the glycolytic products will be metabolized by anaerobic fermentation, a process that is independent of the mitochondria.[14] The production of ATP from glucose has an approximately 13-times higher yield during aerobic respiration compared to fermentation.[69] Recently it has been shown that plant mitochondria can produce a limited amount of ATP without oxygen by using the alternate substrate nitrite.[70] ATP crosses out through the inner membrane with the help of a specific protein, and across the outer membrane via porins. ADP returns via the same route.

text: Pyruvate and the citric acid cycle

text: Pyruvate molecules produced by glycolysis are actively transported across the inner mitochondrial membrane, and into the matrix where they can either be oxidized and combined with coenzyme A to form CO2, acetyl-CoA, and NADH,[14] or they can be carboxylated (by pyruvate carboxylase) to form oxaloacetate. This latter reaction ”fills up” the amount of oxaloacetate in the citric acid cycle, and is therefore an anaplerotic reaction, increasing the cycle’s capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g. in muscle) are suddenly increased by activity.[71]

text: In the citric acid cycle, all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an anaplerotic effect, and its removal has a cataplerotic effect. These anaplerotic and cataplerotic reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases the rate of ATP production by the mitochondrion, and thus the availability of ATP to the cell.[71]

text: Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the beta-oxidation of fatty acids, is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO2 and water, with the energy thus released captured in the form of ATP.[71]

text: In the liver, the carboxylation of cytosolic pyruvate into intra-mitochondrial oxaloacetate is an early step in the gluconeogenic pathway, which converts lactate and de-aminated alanine into glucose,[14][71] under the influence of high levels of glucagon and/or epinephrine in the blood.[71] Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted into cytosolic oxaloacetate, which is ultimately converted into glucose, in a process that is almost the reverse of glycolysis.[71]

text: The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II.[72] The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH2) that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP).[14]

text: NADH and FADH2: the electron transport chain

text: The redox energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle.[14] Protein complexes in the inner membrane (NADH dehydrogenase (ubiquinone), cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H+) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide.[14] This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process.[73]

text: As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (Pi).[14] This process is called chemiosmosis, and was first described by Peter Mitchell[74][75] who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase.[76]

text: Heat production

text: Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat.[14] The process is mediated by a proton channel called thermogenin, or UCP1.[77] Thermogenin is a 33 kDa protein first discovered in 1973.[78] Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.[77]

text: Storage of calcium ions

text: The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium.[79] [80] In fact, their ability to rapidly take in calcium for later release makes them very good "cytosolic buffers" for calcium.[81][82][83] The endoplasmic reticulum (ER) is the most significant storage site of calcium,[55] and there is a significant interplay between the mitochondrion and ER with regard to calcium.[84] The calcium is taken up into the matrix by the mitochondrial calcium uniporter on the inner mitochondrial membrane.[85] It is primarily driven by the mitochondrial membrane potential.[80] Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways.[85] This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells.[86]

text: Ca2+ influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory bioenergetics by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating a reduction of oxidative stress.[87] In neurons, concomitant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of isocitrate dehydrogenase, one of the key regulatory enzymes of the Kreb's cycle.[88]

text: Additional functions

text: Mitochondria play a central role in many other metabolic tasks, such as:

text:
Signaling through mitochondrial reactive oxygen species[89]
Regulation of the membrane potential[14]
Apoptosis-programmed cell death[90]
Calcium signaling (including calcium-evoked apoptosis)[91]
Regulation of cellular metabolism[92]
Certain heme synthesis reactions[93] (see also: porphyrin)
Steroid synthesis.[81]
Hormonal signaling [94] Mitochondria are sensitive and responsive to hormones, in part by the action of mitochondrial estrogen receptors (mtERs). These receptors have been found in various tissues and cell types, including brain [95] and heart [96]

text: Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.

text: Cellular proliferation regulation

text: The relationship between cellular proliferation and mitochondria has been investigated using cervical cancer HeLa cells. Tumor cells require an ample amount of ATP (Adenosine triphosphate) in order to synthesize bioactive compounds such as lipids, proteins, and nucleotides for rapid cell proliferation.[97] The majority of ATP in tumor cells is generated via the oxidative phosphorylation pathway (OxPhos).[98] Interference with OxPhos have shown to cause cell cycle arrest suggesting that mitochondria play a role in cell proliferation.[98] Mitochondrial ATP production is also vital for cell division in addition to other basic functions in the cell including the regulation of cell volume, solute concentration, and cellular architecture.[99][100][101] ATP levels differ at various stages of the cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle.[102] ATP's role in the basic functions of the cell make the cell cycle sensitive to changes in the availability of mitochondrial derived ATP.[102] The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria play an important role in cell cycle regulation.[102] Although the specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division.[103]

text: Genome

text: Mitochondria contain their own genome, an indication that they are derived from bacteria through endosymbiosis. However, the ancestral endosymbiont genome has lost most of its genes so that the mitochondrial genome is one of the most reduced genomes across organisms.

text: The human mitochondrial genome is a circular DNA molecule of about 16 kilobases.[104] It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA (for the 20 standard amino acids, plus an extra gene for leucine and serine), and 2 for rRNA.[104] One mitochondrion can contain two to ten copies of its DNA.[105]

text: As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion.[45] The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. Most mitochondrial genomes are circular, although exceptions have been reported.[106] In general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome;[45] however, introns have been observed in some eukaryotic mitochondrial DNA,[107] such as that of yeast[108] and protists,[109] including Dictyostelium discoideum.[110] Between protein-coding regions, tRNAs are present. During transcription, the tRNAs acquire their characteristic L-shape that gets recognized and cleaved by specific enzymes. Mitochondrial tRNA genes have different sequences from the nuclear tRNAs but lookalikes of mitochondrial tRNAs have been found in the nuclear chromosomes with high sequence similarity.[111]

text: In animals, the mitochondrial genome is typically a single circular chromosome that is approximately 16 kb long and has 37 genes. The genes, while highly conserved, may vary in location. Curiously, this pattern is not found in the human body louse (Pediculus humanus). Instead, this mitochondrial genome is arranged in 18 minicircular chromosomes, each of which is 3–4 kb long and has one to three genes.[112] This pattern is also found in other sucking lice, but not in chewing lice. Recombination has been shown to occur between the minichromosomes. The reason for this difference is not known.

text: Alternative genetic code

text: While slight variations on the standard genetic code had been predicted earlier,[113] none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code.[114] However, the mitochondria of many other eukaryotes, including most plants, use the standard code.[115] Many slight variants have been discovered since,[116] including various alternative mitochondrial codes.[117] Further, the AUA, AUC, and AUU codons are all allowable start codons.

text:
Exceptions to the standard genetic code in mitochondria[13]

Organism
Codon
Standard
Mitochondria

Mammals
AGA, AGG
Arginine
Stop codon

Invertebrates
AGA, AGG
Arginine
Serine

Fungi
CUA
Leucine
Threonine

All of the above
AUA
Isoleucine
Methionine

UGA
Stop codon
Tryptophan

text: Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. In higher plants, it was thought that CGG encoded for tryptophan and not arginine; however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the standard genetic code for tryptophan.[118] Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine.[119]

text: Evolution and diversity

text: Mitochondrial genomes have far fewer genes than the bacteria from which they are thought to be descended. Although some have been lost altogether, many have been transferred to the nucleus, such as the respiratory complex II protein subunits.[104] This is thought to be relatively common over evolutionary time. A few organisms, such as the Cryptosporidium, actually have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred.[120] In Cryptosporidium, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone.[120]

text: Replication and inheritance

text: Mitochondria divide by binary fission, similar to bacterial cell division.[121] The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division is linked to the cell cycle. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in mammals for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When the energy use is low, mitochondria are destroyed or become inactive. In such examples, and in contrast to the situation in many single celled eukaryotes, mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm. Understanding of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in pathologies associated with several disease conditions.[122]

text: The hypothesis of mitochondrial binary fission has relied on the visualization by fluorescence microscopy and conventional transmission electron microscopy (TEM). The resolution of fluorescence microscopy(~200 nm) is insufficient to distinguish structural details, such as double mitochondrial membrane in mitochondrial division or even to distinguish individual mitochondria when several are close together. Conventional TEM has also some technical limitations[which?] in verifying mitochondrial division. Cryo-electron tomography was recently used to visualize mitochondrial division in frozen hydrated intact cells. It revealed that mitochondria divide by budding.[123]

text: An individual's mitochondrial genes are not inherited by the same mechanism as nuclear genes. Typically, the mitochondria are inherited from one parent only. In humans, when an egg cell is fertilized by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. In contrast, the mitochondria, and therefore the mitochondrial DNA, usually come from the egg only. The sperm's mitochondria enter the egg, but do not contribute genetic information to the embryo.[124] Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo.[125] The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited only from mothers, a pattern known as maternal inheritance. This mode is seen in most organisms, including the majority of animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yews.[126] For Mytilids, paternal inheritance only occurs within males of the species.[127][128][129] It has been suggested that it occurs at a very low level in humans.[130] There is a recent suggestion that mitochondria that shorten male lifespan stay in the system because they are inherited only through the mother. By contrast, natural selection weeds out mitochondria that reduce female survival as such mitochondria are less likely to be passed on to the next generation. Therefore, it is suggested that human females and female animals tend to live longer than males. The authors claim that this is a partial explanation.[131]

text: Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA.[105] For this reason, mitochondrial DNA is usually thought to reproduce by binary fission. What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells.[132] Further, evidence suggests that animal mitochondria can undergo recombination.[133] The data are a bit more controversial in humans, although indirect evidence of recombination exists.[134][135] If recombination does not occur, the whole mitochondrial DNA sequence represents a single haplotype, which makes it useful for studying the evolutionary history of populations.

text: Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the inexorable accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this buildup through a developmental process known as the mtDNA bottleneck. The bottleneck exploits stochastic processes in the cell to increase in the cell-to-cell variability in mutant load as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo where different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilisation or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated,[136][137][138] with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell.[139]

text: Population genetic studies

text: The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology.[140] Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve.[141][142] This is often interpreted as strong support for a recent modern human expansion out of Africa.[143] Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for the lack of interbreeding between Neanderthals and anatomically modern humans.[144]

text: However, mitochondrial DNA reflects only the history of the females in a population and so may not represent the history of the population as a whole. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome.[143] In a broader sense, only studies that also include nuclear DNA can provide a comprehensive evolutionary history of a population.[145]

text: Recent measurements of the molecular clock for mitochondrial DNA[146] reported a value of 1 mutation every 7884 years dating back to the most recent common ancestor of humans and apes, which is consistent with estimates of mutation rates of autosomal DNA (10−8 per base per generation[147]).

text: Dysfunction and disease

text: Mitochondrial diseases

text: Damage and subsequent dysfunction in mitochondria is an important factor in a range of human diseases due to their influence in cell metabolism. Mitochondrial disorders often present themselves as neurological disorders, including autism.[12] They can also manifest as myopathy, diabetes, multiple endocrinopathy, and a variety of other systemic disorders.[148] Diseases caused by mutation in the mtDNA include Kearns-Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy.[149] In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and others are due to point mutations in mtDNA.[148]

text: In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease.[150] These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome.[148] Environmental influences may interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease.[151][152] Other pathologies with etiology involving mitochondrial dysfunction include schizophrenia, bipolar disorder, dementia, Alzheimer's disease,[153] Parkinson's disease, epilepsy, stroke, cardiovascular disease, chronic fatigue syndrome, retinitis pigmentosa, and diabetes mellitus.[154][155]

text: Mitochondria-mediated oxidative stress plays a role in cardiomyopathy in Type 2 diabetics. Increased fatty acid delivery to the heart increases fatty acid uptake by cardiomyocytes, resulting in increased fatty acid oxidation in these cells. This process increases the reducing equivalents available to the electron transport chain of the mitochondria, ultimately increasing reactive oxygen species (ROS) production. ROS increases uncoupling proteins (UCPs) and potentiate proton leakage through the adenine nucleotide translocator (ANT), the combination of which uncouples the mitochondria. Uncoupling then increases oxygen consumption by the mitochondria, compounding the increase in fatty acid oxidation. This creates a vicious cycle of uncoupling; furthermore, even though oxygen consumption increases, ATP synthesis does not increase proportionally because the mitochondria is uncoupled. Less ATP availability ultimately results in an energy deficit presenting as reduced cardiac efficiency and contractile dysfunction. To compound the problem, impaired sarcoplasmic reticulum calcium release and reduced mitochondrial reuptake limits peak cytosolic levels of the important signaling ion during muscle contraction. The decreased intra-mitochondrial calcium concentration increases dehydrogenase activation and ATP synthesis. So in addition to lower ATP synthesis due to fatty acid oxidation, ATP synthesis is impaired by poor calcium signaling as well, causing cardiac problems for diabetics.[156]

text: Possible relationships to aging

text: Given the role of mitochondria as the cell's powerhouse, there may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. This was thought to result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA (mtDNA).[157] Hypothesized links between aging and oxidative stress are not new and were proposed in 1956,[158] which was later refined into the mitochondrial free radical theory of aging.[159] A vicious cycle was thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress.

text: A number of changes can occur to mitochondria during the aging process.[160] Tissues from elderly patients show a decrease in enzymatic activity of the proteins of the respiratory chain.[161] However, mutated mtDNA can only be found in about 0.2% of very old cells.[162] Large deletions in the mitochondrial genome have been hypothesized to lead to high levels of oxidative stress and neuronal death in Parkinson's disease.[163]

text: In popular culture

text: Madeleine L'Engle's 1973 science fantasy novel A Wind in the Door prominently features the mitochondria of main character Charles Wallace Murry, as being inhabited by creatures known as the farandolae. The novel also features other characters travelling inside one of Murry's mitochondria.

text: The 1995 horror fiction novel Parasite Eve by Hideaki Sena depicts mitochondria as having some consciousness and mind control abilities, attempting to use these to overtake eukaryotes as the dominant life form. This text was adapted into an eponymous film, video game, and video game sequel all involving a similar premise.

text: In the Star Wars franchise, microorganisms referred to as "midi-chlorians" give some characters the ability to sense and use the Force. George Lucas, director of the 1999 film Star Wars: Episode I – The Phantom Menace, in which midi-chlorians were introduced, described them as "a loose depiction of mitochondria".[164] The non-fictional Midichloria genus of bacteria was later named after the midi-chlorians of Star Wars.

text: As a result of the mitochondrion's prominence in modern science education, the phrase "mitochondria is [sic] the powerhouse of the cell" became a popular Internet meme.[165] The meme is used to imply that secondary education places an insufficient focus on life skills, compared to academic knowledge such as the role of the mitochondrion, which has been considered comparatively impractical.[166]


document_title: OSI model

question_text: what is the seven layers of the osi model

root

text: OSI model

text: History[edit]

text: In the late 1970s, one project was administered by the International Organization for Standardization (ISO), while another was undertaken by the International Telegraph and Telephone Consultative Committee (CCITT, from French: Comité Consultatif International Téléphonique et Télégraphique). These two international standards bodies each developed a document that defined similar networking models.

tag: p

text: In 1983, these two documents were merged to form a standard called The Basic Reference Model for Open Systems Interconnection. The standard is usually referred to as the Open Systems Interconnection Reference Model, the OSI Reference Model, or simply the OSI model. It was published in 1984 by both the ISO, as standard ISO 7498, and the renamed CCITT (now called the Telecommunications Standardization Sector of the International Telecommunication Union or ITU-T) as standard X.200.

text: OSI had two major components, an abstract model of networking, called the Basic Reference Model or seven-layer model, and a set of specific protocols.

text: The concept of a seven-layer model was provided by the work of Charles Bachman at Honeywell Information Services. Various aspects of OSI design evolved from experiences with the ARPANET, NPLNET, EIN, CYCLADES network and the work in IFIP WG6.1. The new design was documented in ISO 7498 and its various addenda. In this model, a networking system was divided into layers. Within each layer, one or more entities implement its functionality. Each entity interacted directly only with the layer immediately beneath it, and provided facilities for use by the layer above it.

text: Protocols enable an entity in one host to interact with a corresponding entity at the same layer in another host. Service definitions abstractly described the functionality provided to an (N)-layer by an (N-1) layer, where N was one of the seven layers of protocols operating in the local host.

text: The OSI standards documents are available from the ITU-T as the X.200-series of recommendations.[1] Some of the protocol specifications were also available as part of the ITU-T X series. The equivalent ISO and ISO/IEC standards for the OSI model were available from ISO. Not all are free of charge.[2]

text: Description of OSI layers[edit]

text: The recommendation X.200 describes seven layers, labeled 1 to 7. Layer 1 is the lowest layer in this model.

text:
OSI Model

Layer

Protocol data unit (PDU)

Function[3]

Hostlayers

7. Application

Data

High-level APIs, including resource sharing, remote file access

6. Presentation

Translation of data between a networking service and an application; including character encoding, data compression and encryption/decryption

5. Session

Managing communication sessions, i.e. continuous exchange of information in the form of multiple back-and-forth transmissions between two nodes

4. Transport

Segment, Datagram

Reliable transmission of data segments between points on a network, including segmentation, acknowledgement and multiplexing

Medialayers

3. Network

Packet

Structuring and managing a multi-node network, including addressing, routing and traffic control

2. Data link

Frame

Reliable transmission of data frames between two nodes connected by a physical layer

1. Physical

Symbol

Transmission and reception of raw bit streams over a physical medium

tag: table

text: At each level N, two entities at the communicating devices (layer N peers) exchange protocol data units (PDUs) by means of a layer N protocol. Each PDU contains a payload, called the service data unit (SDU), along with protocol-related headers or footers.

text: Data processing by two communicating OSI-compatible devices is done as such:

text:
The data to be transmitted is composed at the topmost layer of the transmitting device (layer N) into a protocol data unit (PDU).
The PDU is passed to layer N-1, where it is known as the service data unit (SDU).
At layer N-1 the SDU is concatenated with a header, a footer, or both, producing a layer N-1 PDU. It is then passed to layer N-2.
The process continues until reaching the lowermost level, from which the data is transmitted to the receiving device.
At the receiving device the data is passed from the lowest to the highest layer as a series of SDUs while being successively stripped from each layer's header or footer, until reaching the topmost layer, where the last of the data is consumed.

text: Some orthogonal aspects, such as management and security, involve all of the layers (See ITU-T X.800 Recommendation[4]). These services are aimed at improving the CIA triad - confidentiality, integrity, and availability - of the transmitted data. In practice, the availability of a communication service is determined by the interaction between network design and network management protocols. Appropriate choices for both of these are needed to protect against denial of service.[citation needed]

text: Layer 1: Physical Layer[edit]

text: The physical layer is responsible for the transmission and reception of unstructured raw data between a device and a physical transmission medium. It converts the digital bits into electrical, radio, or optical signals. Layer specifications define characteristics such as voltage levels, the timing of voltage changes, physical data rates, maximum transmission distances, and physical connectors. This includes the layout of pins, voltages, line impedance, cable specifications, signal timing and frequency for wireless devices. Bit rate control is done at the physical layer and may define transmission mode as simplex, half duplex, and full duplex. The components of a physical layer can be described in terms of a network topology. Bluetooth, Ethernet, and USB all have specifications for a physical layer.

text: Layer 2: Data Link Layer[edit]

text:
The data link layer provides node-to-node data transfer—a link between two directly connected nodes.  It detects and possibly corrects errors that may occur in the physical layer.
It defines the protocol to establish and terminate a connection between two physically connected devices. It also defines the protocol for flow control between them.

text: IEEE 802 divides the data link layer into two sublayers:[5]

text:
Medium access control (MAC) layer – responsible for controlling how devices in a network gain access to a medium and permission to transmit data.
Logical link control (LLC) layer – responsible for identifying and encapsulating network layer protocols, and controls error checking and frame synchronization.

tag: ul

text: The MAC and LLC layers of IEEE 802 networks such as 802.3 Ethernet, 802.11 Wi-Fi, and 802.15.4 ZigBee operate at the data link layer.

text: The Point-to-Point Protocol (PPP) is a data link layer protocol that can operate over several different physical layers, such as synchronous and asynchronous serial lines.

text: The ITU-T G.hn standard, which provides high-speed local area networking over existing wires (power lines, phone lines and coaxial cables), includes a complete data link layer that provides both error correction and flow control by means of a selective-repeat sliding-window protocol.

text: Layer 3: Network Layer[edit]

text: The network layer provides the functional and procedural means of transferring variable length data sequences (called packets) from one node to another connected in "different networks". A network is a medium to which many nodes can be connected, on which every node has an address and which permits nodes connected to it to transfer messages to other nodes connected to it by merely providing the content of a message and the address of the destination node and letting the network find the way to deliver the message to the destination node, possibly routing it through intermediate nodes. If the message is too large to be transmitted from one node to another on the data link layer between those nodes, the network may implement message delivery by splitting the message into several fragments at one node, sending the fragments independently, and reassembling the fragments at another node. It may, but does not need to, report delivery errors.

text: Message delivery at the network layer is not necessarily guaranteed to be reliable; a network layer protocol may provide reliable message delivery, but it need not do so.

text: A number of layer-management protocols, a function defined in the management annex, ISO 7498/4, belong to the network layer. These include routing protocols, multicast group management, network-layer information and error, and network-layer address assignment. It is the function of the payload that makes these belong to the network layer, not the protocol that carries them.[6]

text: Layer 4: Transport Layer[edit]

text: The transport layer provides the functional and procedural means of transferring variable-length data sequences from a source to a destination host, while maintaining the quality of service functions.

text: The transport layer controls the reliability of a given link through flow control, segmentation/desegmentation, and error control. Some protocols are state- and connection-oriented. This means that the transport layer can keep track of the segments and re-transmit those that fail delivery. The transport layer also provides the acknowledgement of the successful data transmission and sends the next data if no errors occurred. The transport layer creates segments out of the message received from the application layer. Segmentation is the process of dividing a long message into smaller messages.

text: OSI defines five classes of connection-mode transport protocols ranging from class 0 (which is also known as TP0 and provides the fewest features) to class 4 (TP4, designed for less reliable networks, similar to the Internet). Class 0 contains no error recovery, and was designed for use on network layers that provide error-free connections. Class 4 is closest to TCP, although TCP contains functions, such as the graceful close, which OSI assigns to the session layer. Also, all OSI TP connection-mode protocol classes provide expedited data and preservation of record boundaries. Detailed characteristics of TP0-4 classes are shown in the following table:[7]

text:
Feature name

TP0
TP1
TP2
TP3
TP4

Connection-oriented network

Yes
Yes
Yes
Yes
Yes

Connectionless network

No
No
No
No
Yes

Concatenation and separation

No
Yes
Yes
Yes
Yes

Segmentation and reassembly

Yes
Yes
Yes
Yes
Yes

Error recovery

No
Yes
Yes
Yes
Yes

Reinitiate connectiona

No
Yes
No
Yes
No

Multiplexing / demultiplexing over single virtual circuit

No
No
Yes
Yes
Yes

Explicit flow control

No
No
Yes
Yes
Yes

Retransmission on timeout

No
No
No
No
Yes

Reliable transport service

No
Yes
No
Yes
Yes

a If an excessive number of PDUs are unacknowledged.

text: An easy way to visualize the transport layer is to compare it with a post office, which deals with the dispatch and classification of mail and parcels sent. A post office inspects only the outer envelope of mail to determine its delivery. Higher layers may have the equivalent of double envelopes, such as cryptographic presentation services that can be read by the addressee only. Roughly speaking, tunneling protocols operate at the transport layer, such as carrying non-IP protocols such as IBM's SNA or Novell's IPX over an IP network, or end-to-end encryption with IPsec. While Generic Routing Encapsulation (GRE) might seem to be a network-layer protocol, if the encapsulation of the payload takes place only at the endpoint, GRE becomes closer to a transport protocol that uses IP headers but contains complete Layer 2 frames or Layer 3 packets to deliver to the endpoint. L2TP carries PPP frames inside transport segments.

text: Although not developed under the OSI Reference Model and not strictly conforming to the OSI definition of the transport layer, the Transmission Control Protocol (TCP) and the User Datagram Protocol (UDP) of the Internet Protocol Suite are commonly categorized as layer-4 protocols within OSI.

text: Layer 5: Session Layer[edit]

text: The session layer controls the dialogues (connections) between computers. It establishes, manages and terminates the connections between the local and remote application. It provides for full-duplex, half-duplex, or simplex operation, and establishes checkpointing, adjournment, termination, and restart procedures. The OSI model made this layer responsible for graceful close of sessions, which is a property of the Transmission Control Protocol, and also for session checkpointing and recovery, which is not usually used in the Internet Protocol Suite. The session layer is commonly implemented explicitly in application environments that use remote procedure calls.

text: Layer 6: Presentation Layer[edit]

text: The presentation layer establishes context between application-layer entities, in which the application-layer entities may use different syntax and semantics if the presentation service provides a mapping between them. If a mapping is available, presentation protocol data units are encapsulated into session protocol data units and passed down the protocol stack.

text: This layer provides independence from data representation by translating between application and network formats. The presentation layer transforms data into the form that the application accepts. This layer formats data to be sent across a network. It is sometimes called the syntax layer.[8] The presentation layer can include compression functions.[9] The Presentation Layer negotiates the Transfer Syntax.

text: The original presentation structure used the Basic Encoding Rules of Abstract Syntax Notation One (ASN.1), with capabilities such as converting an EBCDIC-coded text file to an ASCII-coded file, or serialization of objects and other data structures from and to XML.  ASN.1 effectively makes an application protocol invariant with respect to syntax.

text: Layer 7: Application Layer[edit]

text: The application layer is the OSI layer closest to the end user, which means both the OSI application layer and the user interact directly with the software application. This layer interacts with software applications that implement a communicating component. Such application programs fall outside the scope of the OSI model. Application-layer functions typically include identifying communication partners, determining resource availability, and synchronizing communication. When identifying communication partners, the application layer determines the identity and availability of communication partners for an application with data to transmit. The most important distinction in the application layer is the distinction between the application-entity and the application. For example, a reservation website might have two application-entities: one using HTTP to communicate with its users, and one for a remote database protocol to record reservations. Neither of these protocols have anything to do with reservations. That logic is in the application itself.  The application layer per se has no means to determine the availability of resources in the network.

text: Cross-layer functions[edit]

text: Cross-layer functions are services that are not tied to a given layer, but may affect more than one layer. Examples include the following:

text:
Security service (telecommunication)[4] as defined by ITU-T X.800 recommendation.
Management functions, i.e. functions that permit to configure, instantiate, monitor, terminate the communications of two or more entities: there is a specific application-layer protocol, common management information protocol (CMIP) and its corresponding service, common management information service (CMIS), they need to interact with every layer in order to deal with their instances.
Multiprotocol Label Switching (MPLS) MPLS, ATM, and X.25 are 3a protocols. OSI divides the Network Layer into 3 roles: 3a) Subnetwork Access, 3b) Subnetwork Dependent Convergence and 3c) Subnetwork Independent Convergence. It was designed to provide a unified data-carrying service for both circuit-based clients and packet-switching clients which provide a datagram-based service model. It can be used to carry many different kinds of traffic, including IP packets, as well as native ATM, SONET, and Ethernet frames. Sometimes one sees reference to a Layer 2.5.
ARP determines the mapping of an IPv4 address to the underlying MAC address. This is not a translation function. If it were IPv4 and the MAC address would be at the same layer. The implementation of the MAC protocol decodes the MAC PDU and delivers the User-Data to the IP-layer. Because Ethernet is a multi-access media, a device sending a PDU on an Ethernet frame needs to know what IP address maps to what MAC address.
DHCP assigns IPv4 addresses to new systems joining a network. There is no means to derive or obtain an IPv4 address from an Ethernet address.
Domain Name Service is an Application Layer service which is used to look up the IP address of a given domain name.  Once a reply is received from the DNS server, it is then possible to form a Layer 4 connection or flow to the desired host. There are no connections at Layer 3.
Cross MAC and PHY Scheduling is essential in wireless networks because of the time varying nature of wireless channels. By scheduling packet transmission only in favorable channel conditions, which requires the MAC layer to obtain channel state information from the PHY layer, network throughput can be significantly improved and energy waste can be avoided.[10]

text: Interfaces[edit]

text: Neither the OSI Reference Model nor OSI protocols specify any programming interfaces, other than deliberately abstract service specifications. Protocol specifications precisely define the interfaces between different computers, but the software interfaces inside computers, known as network sockets are implementation-specific.

text: For example, Microsoft Windows' Winsock, and Unix's Berkeley sockets and System V Transport Layer Interface, are interfaces between applications (layer 5 and above) and the transport (layer 4). NDIS and ODI are interfaces between the media (layer 2) and the network protocol (layer 3).

text: Interface standards, except for the physical layer to media, are approximate implementations of OSI service specifications.

text: Examples[edit]

text:
Layer

OSI protocols

TCP/IP protocols

SignalingSystem 7[11]

AppleTalk

IPX

SNA

UMTS

Miscellaneous examples

No.
Name

7

Application

FTAMX.400X.500DAPROSERTSEACSE[12]CMIP[13]

INAPMAPTCAPISUPTUP

AFPZIPRTMPNBP

SAP

APPC

HL7ModbusHTTP

6

Presentation

ISO/IEC 8823X.226ISO/IEC 9576-1X.236

MIMESSLTLSXDR

AFP

TDIASCIIEBCDICMIDIMPEG

5

Session

ISO/IEC 8327X.225ISO/IEC 9548-1X.235

Sockets (session establishment in TCP / RTP / PPTP)

ASPADSPPAP

NWLink

DLC?

Named pipesNetBIOSSAPhalf duplexfull duplexsimplexRPCSOCKS

4

Transport

ISO/IEC 8073TP0TP1TP2TP3TP4 (X.224)ISO/IEC 8602X.234

TCPUDPSCTPDCCP

DDPSPX

NBF

3

Network

ISO/IEC 8208X.25 (PLP) ISO/IEC 8878X.223ISO/IEC 8473-1CLNP X.233ISO/IEC 10589IS-IS

IPIPsecICMPIGMPOSPFRIP

SCCPMTP

ATP (TokenTalk / EtherTalk)

IPX

RRC / BMC

NBFQ.931NDPIS-IS

2

Data link

ISO/IEC 7666X.25 (LAPB)Token BusX.222ISO/IEC 8802-2LLC (type 1 / 2)[14]

PPPSBTVSLIP

MTPQ.710

LocalTalkARAPPP

IEEE 802.3 framingEthernet II framing

SDLC

PDCP[15]LLCMAC

ARPARQATMBit stuffingCDPCRCDOCSISFDDIFDPFibre ChannelFrame RelayHDPHDLCIEEE 802.3 (Ethernet)IEEE 802.11a/b/g/n (Ethernet MAC and LLC)IEEE 802.1Q (VLAN)ISLITU-T G.hn DLLLinux interface bondingPPPQ.921Token Ring

1

Physical

X.25 (X.21bisEIA/TIA-232EIA/TIA-449EIA-530G.703)[14]

MTPQ.710

RS-232RS-422PhoneNet

Twinax

UMTS air interfaces

RS-232Full duplexRJ45 (8P8C)V.35V.34I.430I.431T1E110BASE-T100BASE-TX1000BASE-TPOTSSONETSDHDSL802.11a/b/g/n PHYITU-T G.hn PHYCAN busDOCSISDWDMOTN

text: Comparison with TCP/IP model[edit]

text: The design of protocols in the TCP/IP model of the Internet does not concern itself with strict hierarchical encapsulation and layering.[16] RFC 3439 contains a section entitled "Layering considered harmful".[17] TCP/IP does recognize four broad layers of functionality which are derived from the operating scope of their contained protocols: the scope of the software application; the end-to-end transport connection; the internetworking range; and the scope of the direct links to other nodes on the local network.[18]

text: Despite using a different concept for layering than the OSI model, these layers are often compared with the OSI layering scheme in the following way:

text:
The Internet application layer includes the OSI application layer, presentation layer, and most of the session layer.
Its end-to-end transport layer includes the graceful close function of the OSI session layer as well as the OSI transport layer.
The internetworking layer (Internet layer) is a subset of the OSI network layer.
The link layer includes the OSI data link layer and sometimes the physical layers, as well as some protocols of the OSI's network layer.

text: These comparisons are based on the original seven-layer protocol model as defined in ISO 7498, rather than refinements in such things as the internal organization of the network layer document.[citation needed]

text: The presumably strict layering of the OSI model as it is usually described does not present contradictions in TCP/IP, as it is permissible that protocol usage does not follow the hierarchy implied in a layered model. Such examples exist in some routing protocols (for example OSPF), or in the description of tunneling protocols, which provide a link layer for an application, although the tunnel host protocol might well be a transport or even an application-layer protocol in its own right.[citation needed]