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Gene Review

CYC1  -  cytochrome c-1

Homo sapiens

Synonyms: Complex III subunit 4, Complex III subunit IV, Cytochrome b-c1 complex subunit 4, Cytochrome c-1, Cytochrome c1, heme protein, mitochondrial, ...
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Disease relevance of CYC1


Psychiatry related information on CYC1


High impact information on CYC1

  • Cytochrome C-mediated apoptosis [11].
  • In this pathway, a variety of apoptotic stimuli cause cytochrome c release from mitochondria, which in turn induces a series of biochemical reactions that result in caspase activation and subsequent cell death [11].
  • Studies of ET reactions in ruthenium-modified proteins have probed lambda and HAB in several metalloproteins (cytochrome c, myoglobin, azurin) [12].
  • The fraction of mtDNA deletions is significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX-positive neurons, suggesting that mtDNA deletions may be directly responsible for impaired cellular respiration [13].
  • While cytochrome c release and DNA fragmentation are unaffected by the noncleavable p75 mutant, mitochondrial morphology of dying cells is maintained, and loss of plasma membrane integrity is delayed [14].

Chemical compound and disease context of CYC1

  • In contrast, the chain-like heme architecture in Shewanella small tetraheme cytochrome c and soluble fumarate reductase provides a pathway for directional electron transfer [15].
  • Reduced (Fe(II)) Rhodopseudomonas palustris cytochrome c' (Cyt c') is more stable toward unfolding ([GuHCl](1/2) = 2.9(1) M) than the oxidized (Fe(III)) protein ([GuHCl](1/2) = 1.9(1) M) [16].
  • This effect is oligomer length-dependent, and the ability of phosphorothioate homopolymers of thymidine of variable lengths to cause the release of cytochrome c from isolated mitochondria of 518A2 melanoma cells can be correlated with their ability to interact with VDAC [17].
  • Cytochrome c oxidase reaction improves histopathological assessment of zidovudine myopathy [18].
  • Ectopic expression of Noxa in HT1080 fibrosarcoma cells enhanced cellular sensitivity to viral or dsRNA/actinomycin D-induced apoptosis, typified by enhanced cytochrome c release from the mitochondrial to the cytosolic fraction and increased cleavage of caspases 3 and 9 [19].

Biological context of CYC1

  • We show here that mammalian p53 expressed in S. cerevisiae is able to activate transcription of a reporter gene placed under the control of a CYC1 hybrid promoter containing the 33 base pair p53-binding sequence [20].
  • Our results indicate that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis [21].
  • We hypothesize that the inability of HCCS-deficient cells to undergo cytochrome c-mediated apoptosis may push cell death toward necrosis that gives rise to severe deterioration of the affected tissues [22].
  • Rapid electrostatic evolution at the binding site for cytochrome c on cytochrome c oxidase in anthropoid primates [23].
  • Although the deduced amino acid sequence of the 22-kDa subunit is not overtly similar to other known cytochromes, we observed a 31-amino acid stretch of 39% identity with polypeptide I of mitochondrial cytochrome c oxidase centered on a potential heme-coordinating histidine [24].

Anatomical context of CYC1

  • During transduction of an apoptotic (death) signal into the cell, there is an alteration in the permeability of the membranes of the cell's mitochondria, which causes the translocation of the apoptogenic protein cytochrome c into the cytoplasm, which in turn activates death-driving proteolytic proteins known as caspases [21].
  • Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9 and caspase-3 activities [25].
  • Notably, HCT116 cells deficient for Bax and Bak failed to release cytochrome c and showed attenuated activation of caspase-9 (LEHDase) and caspase-3/caspase-7 (DEVDase) upon p14(ARF) expression [26].
  • Prolonged exposure (> or =6 h) of HeLa cells to rottlerin and TNF decreased the level of cytochrome c but not of AIF in the cytosol [27].
  • Here, we examined apoptosis in human endothelial cells, using procaspase-8 and cytochrome c release as markers of the extrinsic and intrinsic pathways, respectively [28].

Associations of CYC1 with chemical compounds

  • Human b5+b5R flavohemoprotein is a NAD(P)H oxidoreductase, demonstrated by superoxide production in the presence of air and excess NAD(P)H and by cytochrome c reduction in vitro [29].
  • We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis [30].
  • Nitric-oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release [30].
  • Treatment of cells with a specific inhibitor of autophagy (3-methyladenine) attenuated localization of LC3 to autophagosomes but exacerbated cytosolic release of cytochrome c as well as apoptotic cell death as revealed by analysis of subdiploid fraction and cytoplasmic histone-associated DNA fragmentation [2].
  • The one-electron reactions led to superoxide formation as detected by cytochrome c reduction and, interestingly, reductive N-denitration of tetryl or 2,4-dinitrophenyl-N-methylnitramine, resulting in the release of nitrite [31].

Physical interactions of CYC1

  • A large scale domain movement involving the iron-sulfur protein subunit is required for electron transfer from cytochrome b-bound ubihydroquinone to cytochrome c1 of the cytochrome bc1 complex [32].
  • Binding of cytochrome c to the cytochrome bc1 complex (complex III) and its subunits cytochrome c1 and b1 [33].

Enzymatic interactions of CYC1

  • After the initial three phases as described previously, cytochrome b becomes oxidized before cytochrome c1 when the limited amount of added substrate is being used up [34].

Regulatory relationships of CYC1


Other interactions of CYC1


Analytical, diagnostic and therapeutic context of CYC1

  • Activation of caspases and mitochondrial release of cytochrome C was determined by immunoblotting [44].
  • After the PDT photoactivation, the release of cytochrome c from the mitochondria to the cytoplasm in a MCF-7 cell was monitored by the optical nanobiosensor inserted inside the single cell and followed by an enzyme-linked immunosorbent assay (ELISA) outside the cell [45].
  • Cytochrome-c reductase (EC from Solanum tuberosum L. comprises ten subunits with apparent molecular sizes of 55, 53, 51, 35, 33, 25, 14, 12, 11 and 10 kDa on 14% SDS-PAGE [46].
  • (Cytochrome c has abnormally low fluorescence, which is not changed by ozone exposure.) The peptides were separated by HPLC [47].
  • Nuclear, cytosolic and mitochondrial fractions were prepared by differential centrifugation and the presence of cytochrome c and lamin B was evaluated by Western blot [48].


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  2. Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells. Herman-Antosiewicz, A., Johnson, D.E., Singh, S.V. Cancer Res. (2006) [Pubmed]
  3. Abundance, subunit composition, redox properties, and catalytic activity of the cytochrome bc1 complex from alkaliphilic and halophilic, photosynthetic members of the family Ectothiorhodospiraceae. Leguijt, T., Engels, P.W., Crielaard, W., Albracht, S.P., Hellingwerf, K.J. J. Bacteriol. (1993) [Pubmed]
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  10. Prodigiosin induces apoptosis by acting on mitochondria in human lung cancer cells. Llagostera, E., Soto-Cerrato, V., Montaner, B., Pérez-Tomás, R. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  11. Cytochrome C-mediated apoptosis. Jiang, X., Wang, X. Annu. Rev. Biochem. (2004) [Pubmed]
  12. Electron transfer in proteins. Gray, H.B., Winkler, J.R. Annu. Rev. Biochem. (1996) [Pubmed]
  13. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Kraytsberg, Y., Kudryavtseva, E., McKee, A.C., Geula, C., Kowall, N.W., Khrapko, K. Nat. Genet. (2006) [Pubmed]
  14. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Ricci, J.E., Muñoz-Pinedo, C., Fitzgerald, P., Bailly-Maitre, B., Perkins, G.A., Yadava, N., Scheffler, I.E., Ellisman, M.H., Green, D.R. Cell (2004) [Pubmed]
  15. Functional roles of the heme architecture and its environment in tetraheme cytochrome C. Akutsu, H., Takayama, Y. Acc. Chem. Res. (2007) [Pubmed]
  16. Cytochrome c' folding triggered by electron transfer: fast and slow formation of four-helix bundles. Lee, J.C., Gray, H.B., Winkler, J.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  17. A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC. Lai, J.C., Tan, W., Benimetskaya, L., Miller, P., Colombini, M., Stein, C.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  18. Cytochrome c oxidase reaction improves histopathological assessment of zidovudine myopathy. Chariot, P., Monnet, I., Gherardi, R. Ann. Neurol. (1993) [Pubmed]
  19. Involvement of Noxa in cellular apoptotic responses to interferon, double-stranded RNA, and virus infection. Sun, Y., Leaman, D.W. J. Biol. Chem. (2005) [Pubmed]
  20. Mammalian p53 can function as a transcription factor in yeast. Schärer, E., Iggo, R. Nucleic Acids Res. (1992) [Pubmed]
  21. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Shimizu, S., Narita, M., Tsujimoto, Y. Nature (1999) [Pubmed]
  22. Mutations of the Mitochondrial Holocytochrome c-Type Synthase in X-Linked Dominant Microphthalmia with Linear Skin Defects Syndrome. Wimplinger, I., Morleo, M., Rosenberger, G., Iaconis, D., Orth, U., Meinecke, P., Lerer, I., Ballabio, A., Gal, A., Franco, B., Kutsche, K. Am. J. Hum. Genet. (2006) [Pubmed]
  23. Rapid electrostatic evolution at the binding site for cytochrome c on cytochrome c oxidase in anthropoid primates. Schmidt, T.R., Wildman, D.E., Uddin, M., Opazo, J.C., Goodman, M., Grossman, L.I. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  24. Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b. Parkos, C.A., Dinauer, M.C., Walker, L.E., Allen, R.A., Jesaitis, A.J., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  25. 3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis. Oh, J.J., Razfar, A., Delgado, I., Reed, R.A., Malkina, A., Boctor, B., Slamon, D.J. Cancer Res. (2006) [Pubmed]
  26. Bak functionally complements for loss of Bax during p14(ARF)-induced mitochondrial apoptosis in human cancer cells. Hemmati, P.G., G??ner, D., Gillissen, B., Wendt, J., von Haefen, C., Chinnadurai, G., D??rken, B., Daniel, P.T. Oncogene (2006) [Pubmed]
  27. Potentiation of tumor necrosis factor-alpha-induced cell death by rottlerin through a cytochrome-C-independent pathway. Basu, A., Johnson, D.E., Woolard, M.D. Exp. Cell Res. (2002) [Pubmed]
  28. S179D Prolactin Primarily Uses the Extrinsic Pathway and Mitogen-Activated Protein Kinase Signaling to Induce Apoptosis in Human Endothelial Cells. Ueda, E.K., Lo, H.L., Bartolini, P., Walker, A.M. Endocrinology (2006) [Pubmed]
  29. Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously expressed in human cells. Zhu, H., Qiu, H., Yoon, H.W., Huang, S., Bunn, H.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  30. Nitric-oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release. Ushmorov, A., Ratter, F., Lehmann, V., Dröge, W., Schirrmacher, V., Umansky, V. Blood (1999) [Pubmed]
  31. Interactions of nitroaromatic compounds with the mammalian selenoprotein thioredoxin reductase and the relation to induction of apoptosis in human cancer cells. Cenas, N., Prast, S., Nivinskas, H., Sarlauskas, J., Arnér, E.S. J. Biol. Chem. (2006) [Pubmed]
  32. Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. Mather, M.W., Darrouzet, E., Valkova-Valchanova, M., Cooley, J.W., McIntosh, M.T., Daldal, F., Vaidya, A.B. J. Biol. Chem. (2005) [Pubmed]
  33. Binding of cytochrome c to the cytochrome bc1 complex (complex III) and its subunits cytochrome c1 and b1. Bosshard, H.R., Zürrer, M., Schägger, H., von Jagow, G. Biochem. Biophys. Res. Commun. (1979) [Pubmed]
  34. Multiphasic oxidation-reduction of cytochrome b in the succinate-cytochrome c reductase. Tsou, C.L., Tang, H.L., Wang, D.C., Jin, Y.Z. Biochim. Biophys. Acta (1982) [Pubmed]
  35. Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Tehranchi, R., Fadeel, B., Forsblom, A.M., Christensson, B., Samuelsson, J., Zhivotovsky, B., Hellstrom-Lindberg, E. Blood (2003) [Pubmed]
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  40. A mitochondrial cytochrome b mutation but no mutations of nuclearly encoded subunits in ubiquinol cytochrome c reductase (complex III) deficiency. Valnot, I., Kassis, J., Chretien, D., de Lonlay, P., Parfait, B., Munnich, A., Kachaner, J., Rustin, P., Rötig, A. Hum. Genet. (1999) [Pubmed]
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  44. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Lügering, A., Schmidt, M., Lügering, N., Pauels, H.G., Domschke, W., Kucharzik, T. Gastroenterology (2001) [Pubmed]
  45. Detection of cytochrome C in a single cell using an optical nanobiosensor. Song, J.M., Kasili, P.M., Griffin, G.D., Vo-Dinh, T. Anal. Chem. (2004) [Pubmed]
  46. Molecular identification of the ten subunits of cytochrome-c reductase from potato mitochondria. Braun, H.P., Kruft, V., Schmitz, U.K. Planta (1994) [Pubmed]
  47. Reaction of ozone with protein tryptophans: band III, serum albumin, and cytochrome C. Mudd, J.B., Dawson, P.J., Tseng, S., Liu, F.P. Arch. Biochem. Biophys. (1997) [Pubmed]
  48. Lovastatin-induced apoptosis in thyroid cells: involvement of cytochrome c and lamin B. Di Matola, T., D'Ascoli, F., Luongo, C., Bifulco, M., Rossi, G., Fenzi, G., Vitale, M. Eur. J. Endocrinol. (2001) [Pubmed]
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