Distinct Roles of Zmynd17 and PGC1α in Mitochondrial Quality Control and Biogenesis in Skeletal Muscle

Abstract

Maintaining skeletal muscle mitochondrial quality is important not only for muscle activity but also for systemic metabolism. Exercise has long been recognized to have a positive impact on muscle mitochondrial quality. Although exercise triggers various changes in the mitochondrial dynamics, its molecular basis remains to be elucidated. We have previously reported that inactivation of the muscle-specific protein, zinc finger MYND domain-containing protein 17 (Zmynd17), results in mitochondrial abnormalities. To investigate the link between Zmynd17 activity and exercise-induced mitochondrial maintenance, we observed the effect of consecutive exercise on the mitochondrial quality in Zmynd17-deficient muscles. Zmynd17-deficient mice displayed abnormal mitochondrial morphology in limb muscles, which remarkably improved upon voluntary exercise. Interestingly, morphological abnormalities in mitochondria were even more apparent when PGC1α, a regulator of exercise-induced mitochondrial biogenesis, was overexpressed in Zmynd17-KO limb muscle. These abnormalities were also ameliorated by voluntary exercise. Our results show that neither the effect of consecutive exercise on mitochondrial quality nor PGC1α-induced mitochondrial biogenesis are mediated through Zmynd17 activity, thereby suggesting the existence of a complex mechanism of mitochondrial quality control in muscles.