The mitochondrial ATP-dependent potassium channel (mitoK ATP ) controls skeletal muscle structure and function.

MitoK ATP is a channel of the inner mitochondrial membrane that controls mitochondrial K + influx according to ATP availability. Recently, the genes encoding the pore-forming (MITOK) and the regulatory ATP-sensitive (MITOSUR) subunits of mitoK ATP were identified, allowing the genetic manipulation of the channel. Here, we analyzed the role of mitoK ATP in determining skeletal muscle structure and activity. Mitok -/- muscles were characterized by mitochondrial cristae remodeling and defective oxidative metabolism, with consequent impairment of exercise performance and altered response to damaging muscle contractions. On the other hand, constitutive mitochondrial K + influx by MITOK overexpression in the skeletal muscle triggered overt mitochondrial dysfunction and energy default, increased protein polyubiquitination, aberrant autophagy flux, and induction of a stress response program. MITOK overexpressing muscles were therefore severely atrophic. Thus, the proper modulation of mitoK ATP activity is required for the maintenance of skeletal muscle homeostasis and function.