Disease relevance of CYC3

• Saccharomyces cerevisiae iso-1-cytochrome c has been expressed in Escherichia coli by coexpression of the genes encoding the cytochrome (CYC1) and yeast cytochrome c heme lyase (CYC3) [1].

High impact information on CYC3

• An open reading frame encoding a protein of 269 amino acids was identified from the DNA sequence of a fragment encompassing the CYC3 gene, and the corresponding transcript shown to be approximately 0.9 kb in length [2].
• Heme in the reduced state is a prerequisite for its covalent attachment to apocytochrome c by the enzyme cytochrome c heme lyase and thus for subsequent translocation of cytochrome c across the outer mitochondrial membrane during import [3].
• Yet, cyc3 mutants contain only apoiso-2-cytochrome c and not apoiso-1-cytochrome c. The lack of accumulation of apoiso-1-cytochrome c in cyc3 mutants, which contain CYC1 mRNA, suggests that apoiso-1-cytochrome c is extensively regulated by a post-transcriptional process [4].
• The cyc3 mutant, which lacks the ability to attach heme groups to apocytochromes c, contains both CYC1 and CYC7 mRNAs in normal amounts [4].
• We postulate that, in vivo, Cyc2p interacts with CCHL and is involved in the reduction of heme prior to its ligation to apocytochrome c by CCHL [5].

Biological context of CYC3

• Both CYC2 and CYC3 are single-copy genes and expressed in all life cycle stages of the parasite [6].
• The nucleotide and the deduced amino acid sequences of this gene displayed 45% homology and 46% identity, respectively, to the Saccharomyces cerevisiae CYC3 gene and shared common features with other reported genes encoding for CCHL [7].
• We show that Cyc2p is required for the activity of CCHL toward apocytochrome c and c1 and becomes essential for the heme attachment to apocytochrome c1 carrying a CAPCH instead of CAACH heme binding site [5].
• In order to examine whether CYC3 associates in vivo with a trypanosome cdc2-related kinase (CRK), the CYC3 gene was fused with the TY-epitope tag, integrated into the trypanosome genome and expressed under inducible control [8].
• Among all respiratory-deficient strains analyzed, cells lacking cytochrome c (cyc3 point mutants) presented the highest level of H(2)O(2) synthesis, indicating that the absence of functional cytochrome c in mitochondria leads to oxidative stress [9].

Anatomical context of CYC3

• Cyc3- mutants lack both holocytochromes c, because of a deficiency of cytochrome c heme lyase, the enzyme catalyzing covalent attachment of the heme group to apocytochrome c. A deficiency of heme lyase also prevents import into mitochondria [10].

Associations of CYC3 with chemical compounds

• Based on the functional interaction of Cyc2p with CCHL and the presence of a putative FAD-binding site in the protein, we hypothesize that Cyc2p controls the redox chemistry of the heme lyase reaction [11].

Regulatory relationships of CYC3

• Here, we demonstrate that yeast CCHL is active toward the non-cognate substrate apocytochrome c1, i.e. CCHL promotes low levels of apocytochrome c1 conversion to its holoform in the absence of CC1HL [11].

Other interactions of CYC3

• Here, we have analyzed the mode of import and folding of the two heme lyases of the yeast Saccharomyces cerevisiae, namely of cytochrome c heme lyase and of cytochrome c1 heme lyase [12].
• This is consistent with the presence in CYC3 of a putative destruction box motif that defines proteins for degradation via the ubiquitin degradation pathway [8].

References