Gene Symbol: Cycs
Description: cytochrome c, somatic
Alias: cytochrome c, somatic
Species: mouse
Products:     Cycs

Top Publications

  1. Hennig B. Change of cytochrome c structure during development of the mouse. Eur J Biochem. 1975;55:167-83 pubmed
  2. Kim I, Nolla H. Antigenic analysis of testicular cytochromes c using monoclonal antibodies. Biochem Cell Biol. 1986;64:1211-7 pubmed
    ..Furthermore, these McAb also reveal that the primary amino acid sequences of cyt ct, which reflect differences in the surface conformation of the molecule, are probably species specific. ..
  3. Hake L, Hecht N. Utilization of an alternative transcription initiation site of somatic cytochrome c in the mouse produces a testis-specific cytochrome c mRNA. J Biol Chem. 1993;268:4788-97 pubmed
    ..Utilization of this alternative initiation site may be involved in the down-regulation of cytochrome cs during spermatogenesis. ..
  4. Vaughn A, Deshmukh M. Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c. Nat Cell Biol. 2008;10:1477-83 pubmed publisher
  5. Mansfield K, Guzy R, Pan Y, Young R, Cash T, Schumacker P, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab. 2005;1:393-9 pubmed
    ..These results provide genetic evidence indicating that mtROS act upstream of prolyl hydroxylases in regulating HIF-1 alpha and HIF-2 alpha in this O(2)-sensing pathway. ..
  6. Potts P, Singh S, Knezek M, Thompson C, Deshmukh M. Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis. J Cell Biol. 2003;163:789-99 pubmed
    ..These data identify a critical function of endogenous XIAP in regulating apoptosis in mammalian cells. ..
  7. Li K, Li Y, Shelton J, Richardson J, Spencer E, Chen Z, et al. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell. 2000;101:389-99 pubmed
    ..In contrast, cells lacking cytochrome c demonstrate increased sensitivity to cell death signals triggered by TNFalpha. These results define the role of cytochrome c in different apoptotic signaling cascades. ..
  8. Sakai T, Liu L, Teng X, Mukai Sakai R, Shimada H, Kaji R, et al. Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis. J Biol Chem. 2004;279:41131-40 pubmed
    ..These findings suggest that Nucling recruits and transports the apoptosome complex during stress-induced apoptosis. ..
  9. Virbasius J, Scarpulla R. Structure and expression of rodent genes encoding the testis-specific cytochrome c. Differences in gene structure and evolution between somatic and testicular variants. J Biol Chem. 1988;263:6791-6 pubmed

More Information


  1. Osborn Heaford H, Ryan A, Murthy S, Racila A, He C, Sieren J, et al. Mitochondrial Rac1 GTPase import and electron transfer from cytochrome c are required for pulmonary fibrosis. J Biol Chem. 2012;287:3301-12 pubmed publisher
    ..These observations demonstrate that mitochondrial import and direct electron transfer from cytochrome c to Rac1 modulates mitochondrial H(2)O(2) production in alveolar macrophages pulmonary fibrosis. ..
  2. Yiu G, Gu W, Hecht N. Heterogeneity in the 5' untranslated region of mouse cytochrome cT mRNAs leads to altered translational status of the mRNAs. Nucleic Acids Res. 1994;22:4599-606 pubmed
  3. Sun Z, Niu R, Wang B, Jiao Z, Wang J, Zhang J, et al. Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo. Arch Toxicol. 2011;85:1441-52 pubmed publisher
    ..Microarray analysis also provided several important biological clues for further investigating fluoride-induced damage in sperm morphology and functions. ..
  4. Owens T, Foster F, Valentijn A, Gilmore A, Streuli C. Role for X-linked Inhibitor of apoptosis protein upstream of mitochondrial permeabilization. J Biol Chem. 2010;285:1081-8 pubmed publisher
    ..Moreover, switching the function of proteins from anti- to proapoptotic forms may be a common theme in the efficient execution of cell death. ..
  5. Ruitenberg M, Kannt A, Bamberg E, Fendler K, Michel H. Reduction of cytochrome c oxidase by a second electron leads to proton translocation. Nature. 2002;417:99-102 pubmed
    ..Here we show that a second electron transfer into the enzyme leads to charge translocation corresponding to pumping of one proton without necessity for a preceding turnover. ..
  6. Jurgensmeier J, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed J. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A. 1998;95:4997-5002 pubmed
  7. Shibata M, Hattori H, Sasaki T, Gotoh J, Hamada J, Fukuuchi Y. Temporal profiles of the subcellular localization of Bim, a BH3-only protein, during middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2002;22:810-20 pubmed
    ..During MCAO, Bad did not show any change in phosphorylation state or subcellular localization. ..
  8. Lakhani S, Masud A, Kuida K, Porter G, Booth C, Mehal W, et al. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 2006;311:847-51 pubmed
    ..Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis. ..
  9. Hake L, Alcivar A, Hecht N. Changes in mRNA length accompany translational regulation of the somatic and testis-specific cytochrome c genes during spermatogenesis in the mouse. Development. 1990;110:249-57 pubmed
    ..7 kb cytochrome cS mRNA is post-meiotically expressed and non-polysomal and (3) cytochrome cS and cytochrome cT mRNAs are each developmentally and translationally regulated during spermatogenesis. ..
  10. Josephs T, Morison I, Day C, Wilbanks S, Ledgerwood E. Enhancing the peroxidase activity of cytochrome c by mutation of residue 41: implications for the peroxidase mechanism and cytochrome c release. Biochem J. 2014;458:259-65 pubmed publisher
    ..These changes enhance access of hydrogen peroxide and substrate to the haem. ..
  11. Liu Z, Lin H, Ye S, Liu Q, Meng Z, Zhang C, et al. Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis. Proc Natl Acad Sci U S A. 2006;103:8965-70 pubmed
    ..Thus, it is very likely that T-Cc has evolved to guarantee the biological integrity of sperm produced in mammalian testis. ..
  12. Wilfling F, Weber A, Potthoff S, Vögtle F, Meisinger C, Paschen S, et al. BH3-only proteins are tail-anchored in the outer mitochondrial membrane and can initiate the activation of Bax. Cell Death Differ. 2012;19:1328-36 pubmed publisher
    ..The recognition of C-terminal membrane-insertion of BH3-only proteins will permit the development of a more detailed concept of the initiation of mitochondrial apoptosis. ..
  13. Diaz F, Thomas C, Garcia S, Hernandez D, Moraes C. Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency. Hum Mol Genet. 2005;14:2737-48 pubmed
    ..This COX10 KO mouse allowed us to correlate the muscle function with residual COX activity, an estimate that can help predict the progression pattern of human mitochondrial myopathies...
  14. Hao Z, Duncan G, Chang C, Elia A, Fang M, Wakeham A, et al. Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell. 2005;121:579-591 pubmed publisher
    ..These studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation. ..
  15. Rajpal A, Cho Y, Yelent B, Koza Taylor P, Li D, Chen E, et al. Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J. 2003;22:6526-36 pubmed
    ..Thus Nur77-mediated apoptosis in T cells involves Bcl-2 independent transcriptional activation of several known and novel apoptotic pathways. ..
  16. Hake L, Kuemmerle N, Hecht N, Kozak C. The genes encoding the somatic and testis-specific isotypes of the mouse cytochrome c genes map to paralogous regions of chromosomes 6 and 2. Genomics. 1994;20:503-5 pubmed
    ..The gene for cytochrome cs, Cycs, maps to a position between Tcrb and Cbl-1 on proximal mouse Chromosome 6, and the gene for cytochrome cT, Cyct, ..
  17. Liang Y, Zhang M, Xia N, Yang Y, Feng L. Effects of high concentration glucose on the expression of NF-kappaB, Bax and cytochrome C and apoptosis of islet cells in mice. J Huazhong Univ Sci Technolog Med Sci. 2009;29:439-44 pubmed publisher
    ..The inhibition of the NF-kappaB expression could be an effective strategy for protecting pancreatic islet cells. ..
  18. De Rocco D, Cerqua C, Goffrini P, Russo G, Pastore A, Meloni F, et al. Mutations of cytochrome c identified in patients with thrombocytopenia THC4 affect both apoptosis and cellular bioenergetics. Biochim Biophys Acta. 2014;1842:269-74 pubmed publisher only one large family from New Zealand and due to a mutation (G41S) of the somatic isoform of the cytochrome c (CYCS) gene. We report a novel CYCS mutation (Y48H) in patients from an Italian family...
  19. Yanamala N, Kapralov A, Djukic M, Peterson J, Mao G, Klein Seetharaman J, et al. Structural re-arrangement and peroxidase activation of cytochrome c by anionic analogues of vitamin E, tocopherol succinate and tocopherol phosphate. J Biol Chem. 2014;289:32488-98 pubmed publisher
    ..Essential for execution of the apoptotic program peroxidase activation of cytochrome c by α-TOS may contribute to its known anti-cancer pharmacological activity. ..
  20. Bakkar N, Ladner K, Canan B, Liyanarachchi S, Bal N, Pant M, et al. IKK? and alternative NF-?B regulate PGC-1? to promote oxidative muscle metabolism. J Cell Biol. 2012;196:497-511 pubmed publisher
    ..Together, these data provide insight on PGC-1? regulation during skeletal myogenesis and reveal a unique function of alternative NF-?B signaling in promoting an oxidative metabolic phenotype. ..
  21. Cleland M, Norris K, Karbowski M, Wang C, Suen D, Jiao S, et al. Bcl-2 family interaction with the mitochondrial morphogenesis machinery. Cell Death Differ. 2011;18:235-47 pubmed publisher
  22. Goldstein J, Munoz Pinedo C, Ricci J, Adams S, Kelekar A, Schuler M, et al. Cytochrome c is released in a single step during apoptosis. Cell Death Differ. 2005;12:453-62 pubmed
    ..c-GFP. We conclude that there is a general mechanism responsible for cytochrome c release that proceeds in a single step that is independent of changes in DeltaPsi(m). ..
  23. Shilov E, Kislyakov I, Gorshkova E, Zvartsev R, Drutskaya M, Mufazalov I, et al. Mouse lymphomyeloid cells can function with significantly decreased expression levels of cytochrome C. Biochemistry (Mosc). 2014;79:1412-22 pubmed publisher
    ..Mice with a complete deficiency of the Cycs gene encoding the somatic cytochrome c die during the embryogenesis...
  24. Karpinich N, Tafani M, Rothman R, Russo M, Farber J. The course of etoposide-induced apoptosis from damage to DNA and p53 activation to mitochondrial release of cytochrome c. J Biol Chem. 2002;277:16547-52 pubmed
    ..The activation of p53 increases Bax synthesis. The translocation of Bax to the mitochondria induces the MPT, the event that releases cytochrome c and culminates in the death of the cells. ..
  25. Vempati U, Han X, Moraes C. Lack of cytochrome c in mouse fibroblasts disrupts assembly/stability of respiratory complexes I and IV. J Biol Chem. 2009;284:4383-91 pubmed publisher
    ..We found that cyt c is associated with both complex IV and respiratory supercomplexes, providing a potential mechanism for the requirement for cyt c in the assembly/stability of complex IV. ..
  26. Carlson S, Mross G, Wilson A, Mead R, Wolin L, Bowers S, et al. Primary structure of mouse, rat, and guinea pig cytochrome c. Biochemistry. 1977;16:1437-42 pubmed
    ..It is concluded that rodent cytochromes c are evolutionarily conservative and that there is no evidence for a generation-time effect in cytochrome c evolution. ..
  27. Tan Z, Sun X, Hou F, Oh H, Hilgenberg L, Hol E, et al. Mutant ubiquitin found in Alzheimer's disease causes neuritic beading of mitochondria in association with neuronal degeneration. Cell Death Differ. 2007;14:1721-32 pubmed
  28. Zhang W, Lu D, Dong W, Zhang L, Zhang X, Quan X, et al. Expression of CYP2E1 increases oxidative stress and induces apoptosis of cardiomyocytes in transgenic mice. FEBS J. 2011;278:1484-92 pubmed publisher
    ..These results demonstrate that CYP2E1 over-expression produces apoptosis and that the up-regulation of CYP2E1 in cTnT(R141W) transgenic mice also correlates with apoptosis in this model. ..
  29. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454:961-7 pubmed publisher
    ..Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis. ..
  30. Limbach K, Wu R. Characterization of a mouse somatic cytochrome c gene and three cytochrome c pseudogenes. Nucleic Acids Res. 1985;13:617-30 pubmed
    ..The other three genes can not properly encode a mouse cytochrome c protein and appear to be pseudogenes which have arisen via an insertion into the mouse genome of a cDNA copy of a cytochrome c mRNA molecule. ..
  31. Van De Pette M, Tunster S, McNamara G, Shelkovnikova T, Millership S, Benson L, et al. Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome. PLoS Genet. 2016;12:e1005916 pubmed publisher
    ..Importantly, active BAT consumes high amounts of energy to generate body heat, providing a valid explanation for the persistence of thinness in our model and supporting a major role for elevated CDKN1C in SRS. ..
  32. Liu D, Lu C, Wan R, Auyeung W, Mattson M. Activation of mitochondrial ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of Bax translocation and cytochrome c release. J Cereb Blood Flow Metab. 2002;22:431-43 pubmed
  33. Josefsson E, Burnett D, Lebois M, Debrincat M, White M, Henley K, et al. Platelet production proceeds independently of the intrinsic and extrinsic apoptosis pathways. Nat Commun. 2014;5:3455 pubmed publisher
    ..Combined loss of Caspase-8/BAK/BAX does not impair thrombopoiesis, but can protect megakaryocytes from death in mice infected with lymphocytic choriomeningitis virus. Thus, apoptosis is dispensable for platelet biogenesis. ..
  34. Lai L, Leone T, Zechner C, Schaeffer P, Kelly S, Flanagan D, et al. Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 2008;22:1948-61 pubmed publisher
    ..We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. ..
  35. Gergalova G, Lykhmus O, Komisarenko S, Skok M. ?7 nicotinic acetylcholine receptors control cytochrome c release from isolated mitochondria through kinase-mediated pathways. Int J Biochem Cell Biol. 2014;49:26-31 pubmed publisher
  36. Kozak C, Gatignol A, Graham K, Jeang K, McBride O. Genetic mapping in human and mouse of the locus encoding TRBP, a protein that binds the TAR region of the human immunodeficiency virus (HIV-1). Genomics. 1995;25:66-72 pubmed
    ..Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells. ..
  37. Ferrer P, Frederick P, Gulbis J, Dewson G, Kluck R. Translocation of a Bak C-terminus mutant from cytosol to mitochondria to mediate cytochrome C release: implications for Bak and Bax apoptotic function. PLoS ONE. 2012;7:e31510 pubmed publisher
    ..In addition, the differential regulation of Bak and Bax by Mcl-1 is predominantly independent of the initial subcellular localizations of Bak and Bax. ..
  38. Kim J, Yang Y, Song S, Na J, Oh K, Jeong C, et al. Beta-amyloid oligomers activate apoptotic BAK pore for cytochrome c release. Biophys J. 2014;107:1601-8 pubmed publisher
    ..Thus, the results suggest that Aβ oligomers function as apoptotic ligands and hijack the intrinsic apoptotic pathway to cause unintended neuronal cell death. ..
  39. Mahapatra G, Varughese A, Ji Q, Lee I, Liu J, Vaishnav A, et al. Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: IMPLICATIONS FOR AMP KINASE. J Biol Chem. 2017;292:64-79 pubmed publisher
  40. Sharma P, Abbasi C, Lazic S, Teng A, Wang D, Dubois N, et al. Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function. Nat Commun. 2015;6:8391 pubmed publisher
    ..Our data demonstrate that the membrane protein Tmem65 is an intercalated disc protein that interacts with and functionally regulates ventricular Cx43. ..
  41. Hashimoto M, Sato T, Muroyama Y, Fujimura L, Hatano M, Saito T. Nepro is localized in the nucleolus and essential for preimplantation development in mice. Dev Growth Differ. 2015;57:529-38 pubmed publisher
    ..These findings indicate that Nepro is a nucleolus-associated protein, and its loss leads to the apoptosis before blastocyst formation in mice. ..
  42. Josephs T, Hibbs M, Ong L, Morison I, Ledgerwood E. Interspecies Variation in the Functional Consequences of Mutation of Cytochrome c. PLoS ONE. 2015;10:e0130292 pubmed publisher
    ..These results have important implications for studies of the effects of cytochrome c mutations on the intrinsic apoptosis pathway. ..
  43. Fernandes R, Tsuda C, Perumalsamy A, Naranian T, Chong J, Acton B, et al. NLRP5 mediates mitochondrial function in mouse oocytes and embryos. Biol Reprod. 2012;86:138, 1-10 pubmed publisher
    ..We therefore conclude that lack of Nlrp5 in oocytes triggers premature activation of the mitochondrial pool, causing mitochondrial damage that cannot be rescued by inactivation of Bax. ..
  44. Gogada R, Prabhu V, Amadori M, Scott R, Hashmi S, Chandra D. Resveratrol induces p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated Bax protein oligomerization on mitochondria to initiate cytochrome c release and caspase activation. J Biol Chem. 2011;286:28749-60 pubmed publisher
    ..Together, our findings characterize the molecular mechanisms of resveratrol-induced caspase activation and subsequent apoptosis in cancer cells. ..
  45. Yang G, Wu L, Chen S, Zhu L, Huang P, Tong L, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs radiation-induced bystander effect. Br J Cancer. 2009;100:1912-6 pubmed publisher
  46. Kanungo A, Hao Z, Elia A, Mak T, Henderson J. Inhibition of apoptosome activation protects injured motor neurons from cell death. J Biol Chem. 2008;283:22105-12 pubmed publisher
    ..Therefore, these results directly demonstrate for the first time the influence of the apoptosome on injury-induced neuronal programmed cell death in vivo isolated from upstream Bcl-2 family-mediated effects. ..
  47. Kapralov A, Kurnikov I, Vlasova I, Belikova N, Tyurin V, Basova L, et al. The hierarchy of structural transitions induced in cytochrome c by anionic phospholipids determines its peroxidase activation and selective peroxidation during apoptosis in cells. Biochemistry. 2007;46:14232-44 pubmed
  48. Vempati U, Diaz F, Barrientos A, Narisawa S, Mian A, Millan J, et al. Role of cytochrome C in apoptosis: increased sensitivity to tumor necrosis factor alpha is associated with respiratory defects but not with lack of cytochrome C release. Mol Cell Biol. 2007;27:1771-83 pubmed
    ..These studies underscore the importance of oxidative phosphorylation and apoptosome function to both the intrinsic and extrinsic apoptotic pathways. ..
  49. Degenhardt K, Sundararajan R, Lindsten T, Thompson C, White E. Bax and Bak independently promote cytochrome C release from mitochondria. J Biol Chem. 2002;277:14127-34 pubmed
    ..Thus, either Bax or Bak is required for death signaling through mitochondria in response to TNF-alpha, but both are dispensable for p53-dependent transformation inhibition. ..