Disproportionate regulation of nuclear- and mitochondrial-encoded cytochrome oxidase subunit proteins by functional activity in neurons.
Cytochrome oxidase is the terminal enzyme in the mitochondrial respiratory chain engaged in oxidative metabolism and energy production. In mammals, the holoenzyme is composed of 13 subunits encoded by both nuclear and mitochondrial genomes. The goal of the present study was to compare the effect of afferent impulse blockade on the expression of these two genomes at the subunit protein level. It also aimed to determine the correlation between the level of cytochrome oxidase activity and the relative amount of subunit proteins. Relative enzyme activity was analysed histochemically, and relative amounts of subunits IV (nuclear-encoded) and II/III (mitochondrial-derived) proteins were obtained immunohistochemically by anti-subunit IV and anti-subunit II/III antibodies in the lateral geniculate nucleus and the primary visual cortex of adult monkeys. In the normal visual centers, similar staining patterns were found for all three markers. After three and seven days of tetrodotoxin treatment, levels of enzyme activity and subunit proteins declined disproportionately in the deprived laminae of the visual center. Densitometric analysis indicates that changes in enzyme activity and subunit IV proteins were significantly greater than those of subunit II/III proteins (P < 0.01). The finding that nuclear and mitochondrial genomes are disproportionately regulated at subunit protein levels by neuronal activity implies that the two genomes operate under different regulatory mechanisms. Changes in subunit IV paralleled most closely those of cytochrome oxidase activity (coefficient of determination r2 = 0.95). This suggests that nuclear-derived subunit IV protein may play a pivotal role in controlling cytochrome oxidase holoenzyme activity.
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D003720:Densitometry; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005829:Geniculate Bodies / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008928:Mitochondria / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014793:Visual Cortex / Q000201:enzymology
D009419:Nerve Tissue Proteins; D013779:Tetrodotoxin; D003576:Electron Transport Complex IV