Difference between revisions of "Cytochrome c" - New World Encyclopedia

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  | AltSymbols =; HCS; CYC
 
  | AltSymbols =; HCS; CYC
 
  | OMIM = 123970
 
  | OMIM = 123970
  | ECnumber =
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  | ECnumber =  
 
  | Homologene = 68675
 
  | Homologene = 68675
 
  | MGIid = 88578
 
  | MGIid = 88578
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  | Process = {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0006309 |text = DNA fragmentation during apoptosis}} {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0008635 |text = caspase activation via cytochrome c}} {{GNF_GO|id=GO:0045333 |text = cellular respiration}}  
 
  | Process = {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0006309 |text = DNA fragmentation during apoptosis}} {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0008635 |text = caspase activation via cytochrome c}} {{GNF_GO|id=GO:0045333 |text = cellular respiration}}  
 
  | Orthologs = {{GNF_Ortholog_box
 
  | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 54205
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  | Hs_EntrezGene = 54205
    | Hs_Ensembl = ENSG00000172115
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  | Hs_Ensembl = ENSG00000172115
    | Hs_RefseqProtein = NP_061820
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  | Hs_RefseqProtein = NP_061820
    | Hs_RefseqmRNA = NM_018947
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  | Hs_RefseqmRNA = NM_018947
    | Hs_GenLoc_db =
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  | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 7
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  | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 25124802
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    | Hs_GenLoc_end = 25131480
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    | Hs_Uniprot = P99999
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  | Hs_Uniprot = P99999
    | Mm_EntrezGene = 13063
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  | Mm_EntrezGene = 13063
    | Mm_Ensembl =
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  | Mm_Ensembl =  
    | Mm_RefseqmRNA = XM_975140
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    | Mm_GenLoc_db =
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}}
'''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.
 
  
==Overview==
+
'''Cytochrome ''c''''', or '''cyt ''c''''' is a small, water soluble [[heme]] [[protein]] associated with the inner [[membrane]] of the [[mitochondrion]]. It is an essential link in the [[electron transport chain]] through which [[cell (biology)|cells]] perform the controlled "burning" of [[glucose]] and capture much of that released energy by storing it in [[ATP]], the cell's primary energy distribution molecule. Each cytochrome ''c'' carries one electron between two different electron transport complexes embedded in the inner membrane. In doing this, cytochrome ''c'' repetitively undergoes either [[oxidation]] or [[redox|reduction]], but it does not bind [[oxygen]].  
'''Cytochromes''' are, in general, membrane-bound [[hemoprotein]]s that contain [[heme]] groups and carry out [[electron transport]].  
 
  
A '''heme''' ([[American English]]) or '''haem''' ([[British English]]) is a [[prosthetic group]] that consists of an [[iron]] atom contained in the center of a large [[heterocyclic]] organic ring called a ''[[porphyrin]]''. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing [[metalloprotein]]s have heme as their prosthetic subunit; these are known as [[hemoprotein]]s.
+
Cytochrome ''c'' has been particularly thoroughly studied because its small size (about 100 [[amino acid]]s) and its water solubility permit researchers to isolate it from other mitochondrial proteins, which tend to be not only larger than cytochrome ''c'' but also fat soluble and embedded in the membrane. These factors combined have led researchers to determine the amino acid sequences for the cytochrome ''c'' occurring in many [[organism]]s from [[yeast]] to [[human]]s.
 +
{{toc}}
 +
Cytochrome ''c'' is found universally in aerobic organisms, and comparison of amino acid sequences of the molecule in diverse species shows a great deal of similarity among [[animal]]s, [[plant]]s, and [[fungi]]. Such similarities suggest a common ancestor that must have been using this protein even before basic divergences between plants and animals arose.  
  
 +
==Overview==
 +
'''Cytochromes''' are, in general, membrane-bound [[hemoprotein]]s that contain [[heme]] groups and carry out [[electron transport]]. A heme ([[American English]]) or haem ([[British English]]) is a [[prosthetic group]] (the non-protein component of an otherwise protein molecular complex) comprising an [[iron]] atom residing in the center of a large [[heterocyclic]] organic molecule called a ''[[porphyrin]]''. Hemoproteins are part of the larger class of [[metalloproteins]], which includes some complexes whose porphyrin prosthetic group contains at its center a different metal atom than iron.
  
 +
Cytochromes are found either as [[subunits|monomeric protein]]s (e.g., cytochrome ''c'') or as subunits of bigger enzymatic complexes that catalyze [[redox]] reactions. They are found in both the [[mitochondrion|mitochondrial]] inner membrane and the [[endoplasmic reticulum]] of [[eukaryote]]s, in the [[chloroplast]]s of plants, in [[photosynthesis|photosynthetic]] [[microorganism]]s, and in [[bacterium|bacteria]].
  
 +
The heme group is a highly-conjugated ring system (which means its [[electron]]s are very mobile) surrounding an iron ion, which readily interconverts between its primary oxidation states. The iron ion interconverts between the Fe<sup>2+</sup> (reduced) and Fe<sup>3+</sup> (oxidized) states in [[electron transfer|electron-transfer]] processes or between the Fe<sup>2+</sup> (reduced) and Fe<sup>3+</sup> (formal, oxidized) states in oxidative processes. Cytochromes are, thus, capable of performing [[redox|oxidation and reduction]]. Because the cytochromes (as well as other complexes) are held within membranes in an organized way, the redox reactions are carried out in the proper sequence for maximum efficiency.
  
They are found either as [[subunits|monomeric protein]]s (e.g., [[cytochrome c]]) or as [[subunits]] of bigger enzymatic complexes that catalyze [[redox]] reactions.  They are found in the [[mitochondrion|mitochondrial]] inner membrane and [[endoplasmic reticulum]] of [[eukaryote]]s, in the [[chloroplast]]s of plants, in [[photosynthesis|photosynthetic]] [[microorganism]]s, and in [[bacterium|bacteria]].
+
In the process of [[oxidative phosphorylation]], which is the '''principal energy-generating process''' undertaken by organisms that need oxygen to survive, other membrane-bound and -soluble [[complex (chemistry)|complex]]es and [[cofactor]]s are involved in the chain of redox reactions, with the additional net effect that protons (H<sup>+</sup>) are transported across the mitochondrial inner membrane into the intermembrane space between the inner and outer membranes. The resulting [[Chemiosmotic potential|transmembrane proton gradient]] (protonmotive force) is used to generate [[adenosine triphosphate|ATP]], which is the universal chemical energy currency of life. ATP is consumed to drive cellular processes that require energy (such as synthesis of macromolecules, active transport of molecules across the membrane, and assembly of [[flagellum|flagella]]).
  
The [[heme]] group is a highly-conjugated ring system (which means its [[electron]]s are very mobile) surrounding a metal ion, which readily interconverts between the oxidation states. For many cytochromes, the metal ion present is that of ''[[iron]]'', which interconverts between Fe<sup>2+</sup> (reduced) and Fe<sup>3+</sup> (oxidized) states ([[electron transfer|electron-transfer]] processes) or between Fe<sup>2+</sup> (reduced) and Fe<sup>3+</sup> (formal, oxidized) states (oxidative processes). Cytochromes are, thus, capable of performing [[redox|oxidation and reduction]]. Because the cytochromes (as well as other complexes) are held within membranes in an organized way, the [[redox]] reactions are carried out in the proper sequence for maximum efficiency.
+
Several kinds of cytochromes exist and can be distinguished by spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential. Three basic types are distinguished by their prosthetic groups: cytochrome ''a'', cytochrome ''b'', and cytochrome ''d''. Cytochrome ''c'', the fourth type of cytochrome, is not defined in terms of the heme group. In [[mitochondrion|mitochondria]] and [[chloroplast]]s, these cytochromes are often combined in [[Electron transfer chain|electron transport]] and related metabolic pathways.
  
In the process of [[oxidative phosphorylation]], which is the principal energy-generating process undertaken by organisms, which need oxygen to survive, other membrane-bound and -soluble [[complex (chemistry)|complex]]es and [[cofactor]]s are involved in the chain of redox reactions, with the additional net effect that protons (H<sup>+</sup>) are transported across the mitochondrial inner membrane. The resulting [[Chemiosmotic potential|transmembrane proton gradient]] ([protonmotive force]) is used to generate [[adenosine triphosphate|ATP]], which is the universal chemical energy currency of life.  ATP is consumed to drive cellular processes that require energy (such as synthesis of macromolecules, active transport of molecules across the membrane, and assembly of [[flagellum|flagella]]).
+
==Description==
 +
'''Cytochromes ''c'' (cytC)''' are electron-transfer proteins having one or several [[heme c]] groups bound to the surrounding protein structure by one or, more generally, two [[thioether]] bonds involving [[sulphydryl]] groups of [[cysteine]] residues. The fifth heme iron [[ligand]] is always provided by a [[histidine]] residue. Cytochromes ''c'' possess a wide range of properties and function in a large number of different redox processes (Pettigrew and Moore 1987).  
  
Several kinds of cytochrome exist and can be distinguished by spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential.
+
Cytochrome c's primary structure comprises a chain of 100 [[amino acid]]s. Its primary function is to transfer electrons between [[Coenzyme Q - cytochrome c reductase|Complexes III]] and [[cytochrome c oxidase|IV]] in the electron transport chain that drives production of ATP..  
  
Three types of cytochrome are distinguished by their prosthetic groups:
+
R. P. Ambler (1991) recognized four classes of cytochrome c:
  
{| class="wikitable"
+
*'''Class I''' includes the [[low­spin]] soluble cytochrome c of [[mitochondria]] and [[bacteria]]. It has the heme-­attachment site toward the N­ terminus of histidine and the sixth ligand provided by a [[methionine]] residue towards the C ­terminus.
| '''Type''' || '''prosthetic group'''
 
|-
 
| Cytochrome a || [[heme a]]
 
|-
 
| Cytochrome b || [[heme b]]
 
|-
 
| Cytochrome d || tetrapyrrolic [[chelate]] of [[iron]]<ref>{{MeshName|Cytochrome+d}}</ref>
 
|}
 
  
The definition of [[cytochrome c]] is not defined in terms of the heme group.<ref>{{MeshName|Cytochrome+c+Group}}.</ref> There is no "cytochrome e," but there is a [[cytochrome f]], which is often considered a type of cytochrome c.<ref>{{eMedicineDictionary|Cytochrome}}</ref>
+
*'''Class II''' includes the [[high­spin]] cytochrome c'. It has the heme-attachment site closed to the N terminus of histidine.  
  
In [[mitochondrion|mitochondria]] and [[chloroplast]]s, these cytochromes are often combined in [[Electron transfer chain|electron transport]] and related metabolic pathways:
+
*'''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="wikitable"
+
*'''Class IV''' was originally created to hold the complex proteins that have other prosthetic groups as well as heme c.
| '''Cytochromes ''' || '''Combination'''
 
|-
 
| ''a'' and ''a<sub>3</sub>'' || [[Cytochrome c oxidase]] ("Complex IV")
 
|-
 
| ''b'' and [[Cytochrome C1|''c<sub>1</sub>'']] || [[Coenzyme Q - cytochrome c reductase]] ("Complex III")
 
|-
 
| ''b<sub>6</sub>'' and [[Cytochrome f|''f'']] || [[Plastoquinol—plastocyanin reductase]]
 
|}
 
  
A completely distinct family of cytochromes is known as the [[cytochrome P450 oxidase]]s, so named for the characteristic [[Soret peak]] formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (with [[sodium dithionite]]) and complexed to [[carbon monoxide]]. These enzymes are primarily involved in [[steroidogenesis]] and [[detoxification]].
+
==Functions==
  
'''Cytochromes ''c'' (cytC)''' are electron-transfer proteins having one or several [[heme c]] groups, bound to the protein by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. Cytochromes ''c'' possess a wide range of properties and function in a large number of different redox processes<ref name="PUB00016291">{{cite journal |author=Moore GR, Pettigrew GW |title= |journal= |volume= |issue= |pages=- |year=1987}}</ref>. The founding member of this family is [[cytochrome c|mitochondrial cytochrome c]].
+
[[Image:ETC.PNG|thumb|right|300px|Electron Transport Chain]]
 +
[[Image:Etc2.png|thumb|right|300px|Mitochondrial Electron Transport Chain]]
  
Ambler<ref name="PUB00000610">{{cite journal |author=Ambler RP |title=Sequence variability in bacterial cytochromes c |journal=Biochim. Biophys. Acta |volume=1058 |issue=1 |pages=42-47 |year=1991 |pmid=1646017}}</ref> recognized four classes of cytC. Class I includes the low-spin soluble cytC of mitochondria and bacteria, with the haem-attachment site towards the N-terminus, and the sixth ligand provided by a methionine residue about 40 residues further on towards the C-terminus. On the basis of sequence similarity, class I cytC were further subdivided into five classes, IA to IE. Class IB includes the eukaryotic mitochondrial cytC and prokaryotic 'short' cyt c2 exemplified by ''[[Rhodopila globiformis]]'' cyt c2; class IA includes 'long' cyt c2, such as ''[[Rhodospirillum rubrum]]'' cyt c2 and ''[[Aquaspirillum itersonii]]'' cytc-550, which have several extra loops by comparison with class IB cytC.
+
===Role in energy metabolism===
 
 
 
 
Its primary structure consists of a chain of 100 [[amino acid]]s.
 
 
 
==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]].
 
 
 
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.  
 
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===
 
===Role in low level laser therapy===
Cytochrome ''c'' is also suspected to be the functional complex in so called LLLT: [[Low-level laser therapy]].
+
Cytochrome ''c'' is also thought to be the functional complex in so called LLLT: [[Low-level laser therapy]]. In LLLT, laser light on the wavelength of 670 nanometers penetrates wounded and scarred tissue and increases 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.
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===
 
===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}}</ref>
+
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 (Liu et al. 1996).
.
 
  
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 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.
+
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 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==
+
==Variation==
In 1991 R. P. Ambler recognized four classes of cytochrome c:
+
[[Image:Cytochrome C.PNG|thumb|right|150px|Cytochrome ''c'', heme shown in red.]]
 
 
*'''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.  
+
The cytochrome ''c'' molecule of diverse organisms has been studied for the glimpse it gives into evolutionary biology. Cytochrome ''c'' is a highly conserved protein across the spectrum of species, found in [[plant]]s, [[animal]]s, and many unicellular [[organism]]s. This, along with its small size (molecular weight about 12,000 [[dalton (unit)|dalton]]s), makes it useful in studies of evolutionary relatedness via [[cladistics]].  
  
*'''Class IV''' was originally created to hold the complex proteins that have other prosthetic groups as well as heme c.
+
The degree of similarities between the cytochrome ''c'' from different species correlates closely with the apparent degree of relatedness between species, e.g. the sequences from [[monkey]]s and [[cattle]] are more similar than the sequences from monkeys and [[fish]]. [[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.
  
 
==References==
 
==References==
<references/>
+
* Ambler, R. P. 1991. [http://www.ncbi.nlm.nih.gov/pubmed/1646017 Sequence variability in bacterial cytochromes c] ''Biochim. Biophys. Acta'' 1058(1): 42-47. Retrieved May 16, 2008.
 +
* Bushnell, G. W., G. V. Louie, and G. D. Brayer. 1990. [http://www.rcsb.org/pdb/cgi/explore.cgi?pid=233461034608315&page=0&pdbId=1HRC High-resolution three-dimensional structure of horse heart cytochrome c] ''J.Mol.Biol.'' 214: 585-595. Retrieved May 16, 2008.
 +
* Liu, X., C. Kim, J. Yang, R. Jemmerson, and X. Wang. 1996. [http://www.ncbi.nlm.nih.gov/pubmed/8689682 Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c] ''Cell'' 86(1): 147-57. Retrieved May 16, 2008.
 +
* Pettigrew, G. W. and G. R. Moore. 1987 ''Cytochromes c: Biological Aspects''. New York: Springer­Verlag. ISBN 0387178430.
  
 
==Further reading==
 
==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==
+
* Broger, C., M. J. Nałecz, and A. Azzi. 1980. [http://www.ncbi.nlm.nih.gov/pubmed/6251869 Interaction of cytochrome c with cytochrome bc1 complex of the mitochondrial respiratory chain] ''Biochim. Biophys. Acta'' 592(3): 519-27. PMID 6251869 Retrieved May 16, 2008.
* [[PEGylation]]
+
* Evans, M. J., and R. C. Scarpulla. 1989. [http://www.ncbi.nlm.nih.gov/pubmed/2849112 The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution] ''Proc. Natl. Acad. Sci. U.S.A.'' 85(24): 9625-9. PMID 2849112 Retrieved May 16, 2008.
 +
* Ferri, K. F., E. Jacotot, J. Blanco, et al. 2001. [http://www.ncbi.nlm.nih.gov/pubmed/11193032 Mitochondrial control of cell death induced by HIV-1-encoded proteins] ''Ann. N. Y. Acad. Sci.'' 926: 149-64. PMID 11193032 Retrieved May 16, 2008.
 +
* Garber, E. A., and E. Margoliash. 1990. [http://www.ncbi.nlm.nih.gov/pubmed/2153405 Interaction of cytochrome c with cytochrome c oxidase: an understanding of the high- to low-affinity transition] ''Biochim. Biophys. Acta'' 1015(2): 279-87. PMID 2153405 Retrieved May 16, 2008.
 +
* Haider, N. N. Narula, and J. Narula. 2003. [http://www.ncbi.nlm.nih.gov/pubmed/12555167 Apoptosis in heart failure represents programmed cell survival, not death, of cardiomyocytes and likelihood of reverse remodeling] ''J. Card. Fail.'' 8(6 Suppl): S512-7. PMID 12555167 Retrieved May 16, 2008.
 +
* Lynch, S. R., D. Sherman, and R. A. Copeland. 1992. [http://www.ncbi.nlm.nih.gov/pubmed/1309738 Cytochrome c binding affects the conformation of cytochrome a in cytochrome c oxidase] ''J. Biol. Chem.'' 267(1): 298-302. PMID 1309738 Retrieved May 16, 2008.
 +
* Mannella, C. A. 1998. [http://www.ncbi.nlm.nih.gov/pubmed/9615439 Conformational changes in the mitochondrial channel protein, VDAC, and their functional implications] ''J. Struct. Biol.'' 121(2): 207-18. PMID 9615439 Retrieved May 16, 2008.
 +
* Michel, B., and H. R. Bosshard. 1984. [http://www.ncbi.nlm.nih.gov/pubmed/6088481 Spectroscopic analysis of the interaction between cytochrome c and cytochrome c oxidase] ''J. Biol. Chem.'' 259(16): 10085-91. PMID 6088481 Retrieved May 16, 2008.
 +
* Skulachev, V. P. 1998. [http://www.ncbi.nlm.nih.gov/pubmed/9515723 Cytochrome c in the apoptotic and antioxidant cascades] ''FEBS Lett.'' 423(3): 275-80. PMID 9515723 Retrieved May 16, 2008.
 +
* Tanaka, Y., T. Ashikari, Y. Shibano, et al. 1988. [http://www.ncbi.nlm.nih.gov/pubmed/2844747 Construction of a human cytochrome c gene and its functional expression in Saccharomyces cerevisiae] ''J. Biochem.'' 103(6): 954-61. PMID 2844747 Retrieved May 16, 2008.
  
==External links==
 
* {{UMichOPM|families|superfamily|78}} - Calculated orientations of cytochromes c in the lipid bilayer
 
* {{MeshName|Cytochrome+c}}
 
  
 
{{Electron transport chain}}
 
{{Electron transport chain}}

Revision as of 16:34, 24 July 2013


Cytochrome c, somatic
Cytochrome c.png
Cytochrome c with heme
Available structures: 1j3s, 2b4z
Identifiers
Symbol(s) CYCS; HCS; CYC
External IDs OMIM: 123970 MGI: 88578 HomoloGene: 68675
RNA expression pattern

PBB GE CYCS 208905 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 54205 13063
Ensembl ENSG00000172115 n/a
Uniprot P99999 n/a
Refseq NM_018947 (mRNA)
NP_061820 (protein)
XM_975140 (mRNA)
XP_980234 (protein)
Location Chr 7: 25.12 - 25.13 Mb n/a
Pubmed search [1] [2]

Cytochrome c, or cyt c is a small, water soluble heme protein associated with the inner membrane of the mitochondrion. It is an essential link in the electron transport chain through which cells perform the controlled "burning" of glucose and capture much of that released energy by storing it in ATP, the cell's primary energy distribution molecule. Each cytochrome c carries one electron between two different electron transport complexes embedded in the inner membrane. In doing this, cytochrome c repetitively undergoes either oxidation or reduction, but it does not bind oxygen.

Cytochrome c has been particularly thoroughly studied because its small size (about 100 amino acids) and its water solubility permit researchers to isolate it from other mitochondrial proteins, which tend to be not only larger than cytochrome c but also fat soluble and embedded in the membrane. These factors combined have led researchers to determine the amino acid sequences for the cytochrome c occurring in many organisms from yeast to humans.

Cytochrome c is found universally in aerobic organisms, and comparison of amino acid sequences of the molecule in diverse species shows a great deal of similarity among animals, plants, and fungi. Such similarities suggest a common ancestor that must have been using this protein even before basic divergences between plants and animals arose.

Overview

Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport. A heme (American English) or haem (British English) is a prosthetic group (the non-protein component of an otherwise protein molecular complex) comprising an iron atom residing in the center of a large heterocyclic organic molecule called a porphyrin. Hemoproteins are part of the larger class of metalloproteins, which includes some complexes whose porphyrin prosthetic group contains at its center a different metal atom than iron.

Cytochromes are found either as monomeric proteins (e.g., cytochrome c) or as subunits of bigger enzymatic complexes that catalyze redox reactions. They are found in both the mitochondrial inner membrane and the endoplasmic reticulum of eukaryotes, in the chloroplasts of plants, in photosynthetic microorganisms, and in bacteria.

The heme group is a highly-conjugated ring system (which means its electrons are very mobile) surrounding an iron ion, which readily interconverts between its primary oxidation states. The iron ion interconverts between the Fe2+ (reduced) and Fe3+ (oxidized) states in electron-transfer processes or between the Fe2+ (reduced) and Fe3+ (formal, oxidized) states in oxidative processes. Cytochromes are, thus, capable of performing oxidation and reduction. Because the cytochromes (as well as other complexes) are held within membranes in an organized way, the redox reactions are carried out in the proper sequence for maximum efficiency.

In the process of oxidative phosphorylation, which is the principal energy-generating process undertaken by organisms that need oxygen to survive, other membrane-bound and -soluble complexes and cofactors are involved in the chain of redox reactions, with the additional net effect that protons (H+) are transported across the mitochondrial inner membrane into the intermembrane space between the inner and outer membranes. The resulting transmembrane proton gradient (protonmotive force) is used to generate ATP, which is the universal chemical energy currency of life. ATP is consumed to drive cellular processes that require energy (such as synthesis of macromolecules, active transport of molecules across the membrane, and assembly of flagella).

Several kinds of cytochromes exist and can be distinguished by spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential. Three basic types are distinguished by their prosthetic groups: cytochrome a, cytochrome b, and cytochrome d. Cytochrome c, the fourth type of cytochrome, is not defined in terms of the heme group. In mitochondria and chloroplasts, these cytochromes are often combined in electron transport and related metabolic pathways.

Description

Cytochromes c (cytC) are electron-transfer proteins having one or several heme c groups bound to the surrounding protein structure by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine residues. The fifth heme iron ligand is always provided by a histidine residue. Cytochromes c possess a wide range of properties and function in a large number of different redox processes (Pettigrew and Moore 1987).

Cytochrome c's primary structure comprises a chain of 100 amino acids. Its primary function is to transfer electrons between Complexes III and IV in the electron transport chain that drives production of ATP..

R. P. Ambler (1991) recognized four classes of cytochrome c:

  • Class I includes the low­spin soluble cytochrome c of mitochondria and bacteria. It has the heme-­attachment site toward 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-attachment 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.

Functions

File:ETC.PNG
Electron Transport Chain
File:Etc2.png
Mitochondrial Electron Transport Chain

Role in energy metabolism

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 thought to be the functional complex in so called LLLT: Low-level laser therapy. In LLLT, laser light on the wavelength of 670 nanometers penetrates wounded and scarred tissue and increases 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.

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 (Liu et al. 1996).

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 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 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.

Variation

File:Cytochrome C.PNG
Cytochrome c, heme shown in red.

The cytochrome c molecule of diverse organisms has been studied for the glimpse it gives into evolutionary biology. 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 daltons), makes it useful in studies of evolutionary relatedness via cladistics.

The degree of similarities between the cytochrome c from different species correlates closely with the apparent degree of relatedness between species, e.g. the sequences from monkeys and cattle are more similar than the sequences from monkeys and fish. Chickens and turkeys have the identical molecule (amino acid for amino acid) within their mitochondria, whereas ducks possess molecules differing by one amino acid. Similarly, both humans and chimpanzees have the identical molecule, while rhesus monkeys possess cytochromes differing by one amino acid.

References
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Further reading


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