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

• DOI: 10.1038/s41419-024-06426-x
• Publication Date: 2024-01-17T06:02:00Z
• Authors: Giulia Di Marco; Gaia Gherardi; Agnese De Mario; Ilaria Piazza; Martina Baraldo; Andrea Mattarei; Bert Blaauw; Rosario Rizzuto; Diego De Stefani; Cristina Mammucari
• Keywords: 0303 health sciences; 03 medical and health sciences; Adenosine Triphosphate; Potassium Channels; QH573-671; Cytology; Muscle, Skeletal; Article; Mitochondria, Heart; Mitochondria

AbstractMitoKATP 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 mitoKATP were identified, allowing the genetic manipulation of the channel. Here, we analyzed the role of mitoKATP 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 mitoKATP activity is required for the maintenance of skeletal muscle homeostasis and function.