Disease relevance of CYC1

• In vivo, depletion of cytochrome c decreases the tumorigenicity of colon cancer cells in syngeneic rats without influencing their growth in immune-deficient animals [1].
• Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells [2].
• Abundance, subunit composition, redox properties, and catalytic activity of the cytochrome bc1 complex from alkaliphilic and halophilic, photosynthetic members of the family Ectothiorhodospiraceae [3].
• Cytochrome c oxidase III was also found to be overexpressed in papillary carcinomas, while the nuclear-encoded mitochondrial transcription factor A showed similar mRNA expression levels in tumor and nontumor tissue [4].
• Fatal infantile mitochondrial myopathy due to cytochrome c oxidase deficiency [5].

Psychiatry related information on CYC1

• The mitochondrial electron transport chain enzyme cytochrome c oxidase (COX) is defective in patients with sporadic Alzheimer's disease (AD) [6].
• In contrast, there was no relationship between either beta-myosin heavy chain or cytochrome C oxidase expression and locomotor activity [7].
• To reveal brain regions most significantly related to individual differences in exploratory behaviour, oxidative metabolism was measured by cytochrome c oxidase histochemistry in 2 months old Wistar rats with persistently high (HE) or low (LE) exploratory activity in a novel environment [8].
• The second patient, a floppy infant with cardiomyopathy and myoclonism, statomotoric and mental retardation showed combined defects in mitochondrial respiratory chain at NADH-CoQ reductase and cytochrome c oxidase and a deficiency of carnitine [9].
• In these cells, we examined mitochondrial apoptosis-inducing factor (AIF) and cytochrome c (cyt c) release to the cytosol in PG time-response studies [10].

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

• G-CSF significantly inhibited cytochrome c release and suppressed apoptosis, most noticeably in cells from patients with sideroblastic anemia [35].
• Moreover, Bak-oligomerization, which is an essential event for tBid-induced cytochrome c release in the extrinsic death signaling pathway, is not associated with Noxa-induced cytochrome c release [36].
• BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria [37].
• Adenoviral melanoma differentiation-associated gene 7 induces apoptosis in lung cancer cells through mitochondrial permeability transition-independent cytochrome c release [38].
• An antioxidant N-acetylcysteine repressed the increases of not only H2O2 but also cytochrome c1 mRNA levels [39].

Other interactions of CYC1

• A mitochondrial cytochrome b mutation but no mutations of nuclearly encoded subunits in ubiquinol cytochrome c reductase (complex III) deficiency [40].
• Mitochondrial hinge protein is a subunit of ubiquinol-cytochrome-c reductase in the respiratory chain and 'hinges' cytochrome c with cytochrome c1 [41].
• Various markers of apoptosis such as Bcl-2, cytochrome C and p53 appear to be involved [42].
• Western blot data revealed that NO gas increased the expressions of anti-apoptosis proteins (Bcl-2 and Mcl-1) and decreased the expression of apoptosis proteins (Bax, t-Bid, cytochrome c, FasL, and caspases) after B[a]P treatment [43].
• These prosthetic groups were associated with three different polypeptides: cytochrome b, cytochrome c1, and the Rieske iron-sulfur protein, with apparent molecular masses of 43, 30, and 21 kDa, respectively [3].

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 1.10.2.2.) 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].

References