Disease relevance of Cyt-c-p

• As the biological action linked to heat stress, 14-3-3zeta interacted with apocytochrome c, a mitochondrial precursor protein of cytochrome c, in heat-treated cells, and the suppression of 14-3-3zeta expression by RNA interference resulted in the formation of significant amounts of aggregated apocytochrome c in the cytosol [1].
• Now we have found that the stability properties of the equivalent mutant of Rhodobacter capsulatus cytochrome c2 (P35A) are somewhat different [2].

High impact information on Cyt-c-p

• In cell-free studies, recombinant DC3 or DC4 failed to activate caspases in Drosophila cell lysates, but remarkably induced caspase activation in extracts from human cells [3].
• The role of cytochrome c in caspase activation in Drosophila melanogaster cells [4].
• Ectopic expression of the proapoptotic Bcl-2 protein, DEBCL, also fails to show any cytochrome c release from mitochondria [4].
• In vitro, DRONC was recruited to a >700-kD complex, similar to the mammalian apoptosome in cell extracts supplemented with cytochrome c and dATP [4].
• The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells [4].

Chemical compound and disease context of Cyt-c-p

• The substitution of proline 35 by alanine in Rhodobacter capsulatus cytochrome c2 affects the overall protein stability but not the alkaline transition [2].

Biological context of Cyt-c-p

• The Drosophila genome contains distinct cyt c genes: cyt c-p and cyt c-d. Loss of cyt c-p function causes embryonic lethality owing to a requirement of the gene for mitochondrial respiration [5].
• These two sequences, DC3 and DC4, have been isolated from a Charon 4A-D. melanogaster genomic library [6].
• DC3 and DC4 are located within a 4 kb region of DNA, at position 36A 10-11, on the left arm of chromosome 2 [6].
• The sequence of fruit fly cytochrome c differed from that reported previously but was identical with that predicted from the nucleotide sequence of the fruit fly cytochrome c gene (DC4) (Limbach, K.J. & Wu, R. (1985) Nucl. Acids Res. 13, 631-644) [7].
• Furthermore, the ratio of cytochrome c to the other cytochromes remains the same at all times, indicating that these components of the respiratory chain follow coordinated developmental programs [8].

Anatomical context of Cyt-c-p

• By using polysome immunoadsorption, a poly(A)+ RNA population of greater than or equal to 95% cytochrome c mRNA was isolated from thoracic muscle tissue and was used to construct a cDNA library, which was screened by hybrid selection/translation [8].
• The cytochrome c oxidase enzyme (COX) is comprised of 10 nuclear-encoded subunits and three mitochondrial-encoded subunits in close physical association in the inner mitochondrial membrane [9].
• The cytochrome P-450 content and the benzo[a]pyrene (BP) hydroxylation, p-nitroanisole demethylation and 3- and 4-hydroxylation of biphenyl were 4-20-fold higher in microsomes from adult flies, while 7-ethoxycoumarin deethylase activity and cytochrome c reductase activity were about the same in the two stages [10].

Associations of Cyt-c-p with chemical compounds

• For example, yeast cells expressing alpha-syn accumulate lipid droplets, have vacuolar/lysosomal defects, and exhibit markers of apoptosis, including the externalization of phosphatidylserine, the release of cytochrome c, and the accumulation of reactive oxygen species [11].
• The valine-substituted rat cytochrome c had properties intermediate between those of the wild type and the alanine mutant [12].
• CoxI RNA also declined with increasing hydrogen peroxide (H2O2) treatment, which was reflected in reduced cytochrome c oxidase (COX) activity [13].
• Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2 [14].

Other interactions of Cyt-c-p

• It harbors the genes for four mitochondrial tRNAs, for cytochrome c oxidase subunits II and III and for ATPase subunits 6 and 8 [15].

Analytical, diagnostic and therapeutic context of Cyt-c-p

• The role of cytochrome c (Cyt c) in caspase activation has largely been established from mammalian cell-culture studies, but much remains to be learned about its physiological relevance in situ [5].
• Strategies for the study of cytochrome c structure and function by site-directed mutagenesis [16].

References