Chromosome 12 Open Reading Frame 65 (C12orf65)

Mitochondrial DNA encodes 13 proteins of oxidative phosphorylation, and these are translated on dedicated mitochondrial ribosomes with translation machinery that resembles that of prokaryotes. C12ORF65 encodes a protein that is critical for the release of newly synthesized proteins from mitochondrial ribosomes. C12ORF65-mutant fibroblasts cultured from 2 patients with a combined oxidative phosphorylation deficiency (COXPD7) showed global and uniform defect in translation of mitochondrial DNA-encoded proteins, resulting in a severe decrease of oxidative phosphorylation complexes I, IV, and V, and a small decrease in complex III. Expression of wildtype C12ORF65 rescued the defect, and overexpression of the mitochondrial release factor ICT1 partly rescued the defect, suggesting C12ORF65 may have a role in releasing peptides from mitochondrial ribosomes.