Skeletal muscle unloading results in increased mitophagy and decreased mitochondrial biogenesis regulation

• Published in: Muscle & nerve Vol. 60; no. 6; pp. 769 - 778
• Main Authors: Leermakers, Pieter A., Kneppers, Anita E.M., Schols, Annemie M.W.J., Kelders, Marco C.J.M., Theije, Chiel C., Verdijk, Lex B., Loon, Luc J.C., Langen, Ramon C.J., Gosker, Harry R.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2019; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Animals; Autophagy; Basic Science; Basic Science s; Biosynthesis; Casts, Surgical; Gastrocnemius muscle; Gene Expression; Hindlimb Suspension; Humans; Immobilization; inactivity; Male; Markers; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria, Muscle - metabolism; Mitochondria, Muscle - pathology; mitochondrial biogenesis; Mitophagy; Mitophagy - genetics; Mitophagy - physiology; Molecular modelling; muscle unloading; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Musculoskeletal system; Organelle Biogenesis; Phagocytosis; Quadriceps Muscle - metabolism; Quadriceps Muscle - pathology; Skeletal muscle; Unloading; Weight-Bearing; Young Adult; mitophagy; skeletal muscle; mitochondrial biogenesis; mitochondria; inactivity; muscle unloading
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.26702

Introduction Physical inactivity significantly contributes to loss of muscle mass and performance in bed‐bound patients. Loss of skeletal muscle mitochondrial content has been well‐established in muscle unloading models, but the underlying molecular mechanism remains unclear. We hypothesized that apparent unloading‐induced loss of muscle mitochondrial content is preceded by increased mitophagy‐ and decreased mitochondrial biogenesis‐signaling during the early stages of unloading. Methods We analyzed a comprehensive set of molecular markers involved in mitochondrial‐autophagy, −biogenesis, −dynamics, and ‐content, in the gastrocnemius muscle of C57BL/6J mice subjected to 0‐ and 3‐days hind limb suspension, and in biopsies from human vastus lateralis muscle obtained before and after 7 days of one‐leg immobilization. Results In both mice and men, short‐term skeletal muscle unloading results in molecular marker patterns indicative of increased receptor‐mediated mitophagy and decreased mitochondrial biogenesis regulation, before apparent loss of mitochondrial content. Discussion These results emphasize the early‐onset of skeletal muscle disuse‐induced mitochondrial remodeling.