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 SDHC (succinate dehydrogenase 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 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 suggest that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema–driven skeletal muscles, which could be impactful in developing strategies aimed at attenuating this comorbidity.

肺气肿患者经常出现运动肌功能障碍，这与该人群的残疾和较高死亡率独立相关。肌肉功能障碍导致产生力的能力降低，这部分取决于纤维的氧化潜力，但很少有机制研究集中在肺气肿的肌肉呼吸上。使用最近建立的肺气肿驱动的骨骼肌功能障碍动物模型，我们发现 SDHC（琥珀酸脱氢酶亚基 C）的下调与运动肌肉的耗氧量和疲劳耐受性降低有关。之前在肺气肿患者的肌肉中观察到 SDH 活性降低，我们发现 SDHC 是支持培养的肌肉细胞呼吸所必需的。而且，肺气肿动物肌肉中SDH功能的体内获得导致更好的耗氧率和疲劳耐受性。这些变化与更多数量相对较多的氧化型 2-A 和 2X 纤维以及数量减少的 2B 纤维相关。我们的数据表明，SDHC 是肺气肿驱动的骨骼肌呼吸和易疲劳性的关键调节因子，这可能对制定旨在减轻这种合并症的策略产生影响。