Quantitative decrease of human cytochrome c oxidase during development: evidences for a post-transcriptional regulation.
In an earlier study, we showed that cytochrome c oxidase activity, measured in mitochondria isolated from human muscular biopsies, decreased steadily and substantially between the age of four years and adulthood (P < 0.05), whereas complexes I and III activity remained constant. The present study investigates a number of possible causes for this change in activity: although there is a drop in the apparent Vmax, neither the apparent enzyme Km, nor the cellular mtDNA concentration shows any variations over the studied period. Steady-state concentrations of mitochondrial gene transcripts (CO I. CO II, CO III, but also 12S, cytochrome b, or ND4) increase within this age group, indicating an overall increase in mitochondrial genome expression. Concentrations of transcripts of nuclear genes CO IV, CO Vb, and CO VIaH likewise show an increase, albeit less marked. On the other hand, heme aa3 levels and concentrations of mitochondrial (CO II) or nuclear (CO IV, CO VIIaH) subunits, estimated using specific antibodies, correlate closely with enzymatic activity and show a parallel decrease between 4 and 20 years. The observed decrease in complex IV activity is thus quantitative, and subject to post-transcriptional and/or post-translational regulation.