RT Journal Article
SR Electronic
T1 Succinate Dehydrogenase (SDH)-subunit C regulates muscle oxygen consumption and fatigability in an animal model of pulmonary emphysema
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.22.427763
DO 10.1101/2021.01.22.427763
A1 Joseph Balnis
A1 Lisa A. Drake
A1 Catherine E. Vincent
A1 Tanner C. Korponay
A1 Diane V. Singer
A1 David Lacomis
A1 Chun Geun Lee
A1 Jack A. Elias
A1 Harold A. Singer
A1 Ariel Jaitovich
YR 2021
UL http://biorxiv.org/content/early/2021/01/22/2021.01.22.427763.abstract
AB Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force-generation capacity which partially depends on fibers’ oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of succinate dehydrogenase (SDH) subunit C in association with lower oxygen consumption and fatigue-tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema and we found that SDHC is required to support respiration in cultured muscle cells. Moreover, in-vivo gain of SDH function in emphysema animals muscles resulted in better oxygen consumption rate (OCR) and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers, and a reduced amount of 2B fibers. Our data suggests that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful to develop strategies aimed at attenuating this comorbidity.Competing Interest StatementThe authors have declared no competing interest.