Cytochrome c 92388 224250193 2008-07-08T00:13:31Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{PBB|geneid=54205}} {{TOCleft}}'''Cytochrome ''c''''', or '''cyt ''c''''' (horse heart: [[Protein data bank|PDB]] [http://www.rcsb.org/pdb/cgi/explore.cgi?pid=233461034608315&page=0&pdbId=1HRC 1HRC]) is a small [[heme]] [[protein]] found loosely associated with the inner membrane of the [[mitochondrion]]. It is a soluble protein, unlike other [[cytochrome]]s, and is an essential component of the [[electron transfer chain]], where it carries one electron. It is capable of undergoing [[oxidation]] and [[redox|reduction]], but does not bind [[oxygen]]. It transfers electrons between [[Coenzyme Q - cytochrome c reductase|Complexes III]] and [[cytochrome c oxidase|IV]]. It belongs to [[cytochrome c family]] of proteins. ==Variation== [[Image:Cytochrome C.PNG|thumb|left|150px|Cytochrome ''c'', heme shown in red.]] Cytochrome c is a highly conserved protein across the spectrum of species, found in plants, animals, and many unicellular organisms. This, along with its small size (molecular weight about 12,000 [[dalton (unit)|dalton]]s), makes it useful in studies of [[cladistics]]. Its primary structure consists of a chain of 100 [[amino acid]]s. The cytochrome ''c'' molecule has been studied for the glimpse it gives into evolutionary biology. Both [[chicken]]s and [[turkey]]s have the identical molecule (amino acid for amino acid) within their mitochondria, whereas [[duck]]s possess molecules differing by one amino acid. Similarly, both [[human]]s and [[chimpanzee]]s have the identical molecule, while [[rhesus monkeys]] possess cytochromes differing by one amino acid. ==Functions== Cytochrome ''c'' can catalyze several reactions such as [[hydroxylation]] and [[aromatic]] [[oxidation]], and shows [[peroxidase]] activity by oxidation of various electron donors such as 2,2-azino-''bis''(3-ethylbenzthiazoline-6-sulphonic acid) ([[ABTS]]), 2-keto-4-thiomethyl butyric acid and 4-aminoantipyrine. ===Role in low level laser therapy=== Cytochrome ''c'' is also suspected to be the functional complex in so called LLLT: [[Low-level laser therapy]]. In LLLT, laser light on the wavelength of 670 nanometer penetrates wounded and scarred tissue in order to increase cellular regeneration. Light of this wavelength appears capable of increasing activity of cytochrome ''c'', thus increasing metabolic activity and freeing up more energy for the cells to repair the tissue.{{Fact|date=April 2008}} ===Role in apoptosis=== Cytochrome ''c'' is also an intermediate in [[apoptosis]], a controlled form of cell death used to kill cells in the process of development or in response to infection or DNA damage<ref>{{cite journal |author=Liu X, Kim C, Yang J, Jemmerson R, Wang X |title=Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c |journal=Cell |volume=86 |issue=1 |pages=147–57 |year=1996 |pmid=8689682 |doi=10.1016/S0092-8674(00)80085-9}}</ref> . Cytochrome ''c'' is released by the mitochondria in response to pro-apoptotic stimuli. The sustained elevation in [[calcium]] levels precedes cyt ''c'' release from the mitochondria. The release of small amounts of cyt ''c'' leads to an interaction with the [[Inositol triphosphate receptor|IP3 receptor]] (IP3R) on the [[endoplasmic reticulum]] (ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt ''c'', which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs. This explains how the ER calcium release can reach cytotoxic levels. This release of cytochrome c in turn activates [[caspase]] 9, a cysteine [[protease]]. Caspase 9 can then go on to activate caspases 3 and 7, which are responsible for destroying the cell from within. ==Classes== In 1991 R. P. Ambler recognized four classes of cytochrome c: *'''Class I''' includes the low­spin soluble cytochrome c of mitochondria and bacteria. It has the heme-­attachment site towards the N­ terminus of histidine and the sixth ligand provided by a methionine residue towards the C ­terminus. *'''Class II''' includes the high­spin cytochrome c'. It has the heme-m­attachment site closed to the N terminus of histidine. *'''Class III''' comprises the low redox potential multiple­ heme cytochromes. The heme c groups are structurally and functionally nonequivalent and present different redox potentials in the range 0 to -400 mV. *'''Class IV''' was originally created to hold the complex proteins that have other prosthetic groups as well as heme c. ==References== <references/> ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=Skulachev VP |title=Cytochrome c in the apoptotic and antioxidant cascades. |journal=FEBS Lett. |volume=423 |issue= 3 |pages= 275–80 |year= 1998 |pmid= 9515723 |doi= }} *{{cite journal | author=Mannella CA |title=Conformational changes in the mitochondrial channel protein, VDAC, and their functional implications. |journal=J. Struct. Biol. |volume=121 |issue= 2 |pages= 207–18 |year= 1998 |pmid= 9615439 |doi= 10.1006/jsbi.1997.3954 }} *{{cite journal | author=Ferri KF, Jacotot E, Blanco J, ''et al.'' |title=Mitochondrial control of cell death induced by HIV-1-encoded proteins. |journal=Ann. N. Y. Acad. Sci. |volume=926 |issue= |pages= 149–64 |year= 2001 |pmid= 11193032 |doi= }} *{{cite journal | author=Britton RS, Leicester KL, Bacon BR |title=Iron toxicity and chelation therapy. |journal=Int. J. Hematol. |volume=76 |issue= 3 |pages= 219–28 |year= 2002 |pmid= 12416732 |doi= }} *{{cite journal | author=Haider N, Narula N, Narula J |title=Apoptosis in heart failure represents programmed cell survival, not death, of cardiomyocytes and likelihood of reverse remodeling. |journal=J. Card. Fail. |volume=8 |issue= 6 Suppl |pages= S512–7 |year= 2003 |pmid= 12555167 |doi= 10.1054/jcaf.2002.130034 }} *{{cite journal | author=Castedo M, Perfettini JL, Andreau K, ''et al.'' |title=Mitochondrial apoptosis induced by the HIV-1 envelope. |journal=Ann. N. Y. Acad. Sci. |volume=1010 |issue= |pages= 19–28 |year= 2004 |pmid= 15033690 |doi= }} *{{cite journal | author=Ng S, Smith MB, Smith HT, Millett F |title=Effect of modification of individual cytochrome c lysines on the reaction with cytochrome b5. |journal=Biochemistry |volume=16 |issue= 23 |pages= 4975–8 |year= 1977 |pmid= 199233 |doi= }} *{{cite journal | author=Lynch SR, Sherman D, Copeland RA |title=Cytochrome c binding affects the conformation of cytochrome a in cytochrome c oxidase. |journal=J. Biol. Chem. |volume=267 |issue= 1 |pages= 298–302 |year= 1992 |pmid= 1309738 |doi= }} *{{cite journal | author=Garber EA, Margoliash E |title=Interaction of cytochrome c with cytochrome c oxidase: an understanding of the high- to low-affinity transition. |journal=Biochim. Biophys. Acta |volume=1015 |issue= 2 |pages= 279–87 |year= 1990 |pmid= 2153405 |doi= }} *{{cite journal | author=Bedetti CD |title=Immunocytochemical demonstration of cytochrome c oxidase with an immunoperoxidase method: a specific stain for mitochondria in formalin-fixed and paraffin-embedded human tissues. |journal=J. Histochem. Cytochem. |volume=33 |issue= 5 |pages= 446–52 |year= 1985 |pmid= 2580882 |doi= }} *{{cite journal | author=Tanaka Y, Ashikari T, Shibano Y, ''et al.'' |title=Construction of a human cytochrome c gene and its functional expression in Saccharomyces cerevisiae. |journal=J. Biochem. |volume=103 |issue= 6 |pages= 954–61 |year= 1988 |pmid= 2844747 |doi= }} *{{cite journal | author=Evans MJ, Scarpulla RC |title=The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 24 |pages= 9625–9 |year= 1989 |pmid= 2849112 |doi= }} *{{cite journal | author=Passon PG, Hultquist DE |title=Soluble cytochrome b 5 reductase from human erythrocytes. |journal=Biochim. Biophys. Acta |volume=275 |issue= 1 |pages= 62–73 |year= 1972 |pmid= 4403130 |doi= }} *{{cite journal | author=Dowe RJ, Vitello LB, Erman JE |title=Sedimentation equilibrium studies on the interaction between cytochrome c and cytochrome c peroxidase. |journal=Arch. Biochem. Biophys. |volume=232 |issue= 2 |pages= 566–73 |year= 1984 |pmid= 6087732 |doi= }} *{{cite journal | author=Michel B, Bosshard HR |title=Spectroscopic analysis of the interaction between cytochrome c and cytochrome c oxidase. |journal=J. Biol. Chem. |volume=259 |issue= 16 |pages= 10085–91 |year= 1984 |pmid= 6088481 |doi= }} *{{cite journal | author=Broger C, Nałecz MJ, Azzi A |title=Interaction of cytochrome c with cytochrome bc1 complex of the mitochondrial respiratory chain. |journal=Biochim. Biophys. Acta |volume=592 |issue= 3 |pages= 519–27 |year= 1980 |pmid= 6251869 |doi= }} *{{cite journal | author=Smith HT, Ahmed AJ, Millett F |title=Electrostatic interaction of cytochrome c with cytochrome c1 and cytochrome oxidase. |journal=J. Biol. Chem. |volume=256 |issue= 10 |pages= 4984–90 |year= 1981 |pmid= 6262312 |doi= }} *{{cite journal | author=Geren LM, Millett F |title=Fluorescence energy transfer studies of the interaction between adrenodoxin and cytochrome c. |journal=J. Biol. Chem. |volume=256 |issue= 20 |pages= 10485–9 |year= 1981 |pmid= 6270113 |doi= }} *{{cite journal | author=Favre B, Zolnierowicz S, Turowski P, Hemmings BA |title=The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo. |journal=J. Biol. Chem. |volume=269 |issue= 23 |pages= 16311–7 |year= 1994 |pmid= 8206937 |doi= }} *{{cite journal | author=Gao B, Eisenberg E, Greene L |title=Effect of constitutive 70-kDa heat shock protein polymerization on its interaction with protein substrate. |journal=J. Biol. Chem. |volume=271 |issue= 28 |pages= 16792–7 |year= 1996 |pmid= 8663341 |doi= }} }} {{refend}} ==Additional images== <gallery> Image:ETC.PNG|ETC Image:Etc2.png|ETC </gallery> ==See also== * [[PEGylation]] ==External links== * {{UMichOPM|families|superfamily|78}} - Calculated orientations of cytochromes c in the lipid bilayer * {{MeshName|Cytochrome+c}} {{Electron transport chain}} [[Category:Cellular respiration]] [[Category:Cytochromes]] [[Category:Programmed cell death]] [[Category:Peripheral membrane proteins]] [[de:Cytochrom c]] [[es:Citocromo c]] [[fr:Cytochrome C]] [[it:Citocromo c]] [[mk:Цитохром c]] [[pl:Cytochrom c]] [[pt:Citocromo c]] [[ru:Цитохром c]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = yes | update_citations = yes }}