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- Title
The mitochondrial ATP-dependent potassium channel (mitoK<sub>ATP</sub>) controls skeletal muscle structure and function.
- Authors
Di Marco, Giulia; Gherardi, Gaia; De Mario, Agnese; Piazza, Ilaria; Baraldo, Martina; Mattarei, Andrea; Blaauw, Bert; Rizzuto, Rosario; De Stefani, Diego; Mammucari, Cristina
- Abstract
MitoKATP 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.
- Publication
Cell Death & Disease, 2024, Vol 15, Issue 1, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-024-06426-x