Succinate dehydrogenase–complex II regulates skeletal muscle cellular respiration and contractility but not muscle mass in genetically induced pulmonary emphysema

• DOI: 10.1126/sciadv.ado8549
• Publication Date: 2024-08-21T22:27:22Z
• Authors: Joseph Balnis; Ankita Tufts; Emily L. Jackson; Lisa A. Drake; Diane V. Singer; David Lacomis; Chun Geun Lee; Jack A. Elias; Jason D. Doles; L. James Maher; Annie Jen; Joshua J. Coon; David Jourd’heuil; Harold A. Singer; Catherine E. Vincent; Ariel Jaitovich
• Keywords: Contractility

Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema are independently associated higher mortality. If reduced cellular respiration contributes to atrophy that setting remains unknown. Using a mouse genetically induced recapitulates dysfunction, we found activity of succinate dehydrogenase (SDH) is hallmark its myopathic changes. We generated an inducible, muscle-specific SDH knockout demonstrates lower mitochondrial oxygen consumption, myofiber contractility, exercise endurance. Respirometry analyses show vitro complex I unaffected by loss subunit C mitochondria, which consistent the animal data. initially causes accumulation down-regulated transcriptome but modest proteome effects. Muscle mass, type composition, overall body constituents remain unaltered transgenic mice. Thus, while regulates experimental emphysema, it does not control or other constituents.