Balnis 2024 Sci Adv
| Balnis J, Tufts A, Jackson EL, Drake LA, Singer DV, Lacomis D, Lee CG, Elias JA, Doles JD, Maher LJ 3rd, Jen A, Coon JJ, Jourd'heuil D, Singer HA, Vincent CE, Jaitovich A (2024) Succinate dehydrogenase-complex II regulates skeletal muscle cellular respiration and contractility but not muscle mass in genetically induced pulmonary emphysema. Sci Adv [Epub ahead of print]. https://doi.org/10.1126/sciadv.ado8549 |
Balnis Joseph, Tufts Ankita, Jackson Emily L, Drake Lisa A, Singer Diane V, Lacomis David, Lee Chun Geun, Elias Jack A, Doles Jason D, Maher 3rd L James, Jen Annie, Coon Joshua J, Jourd'heuil David, Singer Harold A, Vincent Catherine E, Jaitovich Ariel (2024) Sci Adv
Abstract: Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes. We generated an inducible, muscle-specific SDH knockout mouse that demonstrates lower mitochondrial oxygen consumption, myofiber contractility, and exercise endurance. Respirometry analyses show that in vitro complex I respiration is unaffected by loss of SDH subunit C in muscle mitochondria, which is consistent with the pulmonary emphysema animal data. SDH knockout initially causes succinate accumulation associated with a down-regulated transcriptome but modest proteome effects. Muscle mass, myofiber type composition, and overall body mass constituents remain unaltered in the transgenic mice. Thus, while SDH regulates myofiber respiration in experimental pulmonary emphysema, it does not control muscle mass or other body constituents.
• Bioblast editor: Plangger M
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Other
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue Enzyme: Complex II;succinate dehydrogenase
Coupling state: ET, LEAK, OXPHOS Pathway: N, S, NS HRR: Oxygraph-2k
2024-09
