PDF(Pubmed)
Abstract：
Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O2 levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O2 levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.
摘要：
线粒体呼吸延伸到ATP生成之外，细胞器参与许多细胞和生理过程。线粒体电子转移系统的组成部分随呼吸的平行变化使其成为协调细胞适应氧气水平变化的适当枢纽。功能性缺氧下呼吸如何变化(即，当细胞内O2水平限制线粒体呼吸时）通过电子转移系统中继以影响线粒体适应和缺氧暴露后的重塑仍然不明确。这在很大程度上是由于在体育锻炼期间将孤立的线粒体的功能与人类联系起来的研究中，在受控和定义的O2水平下整合发现的挑战。在这里，我们介绍了在离体线粒体缺氧条件下的实验，肌管和锻炼人类。用孤立的线粒体进行稳态呼吸测定，我们发现呼吸的氧限制减少了电子流和氧化磷酸化，降低了线粒体膜电位差异，和减少线粒体钙流入。同样，在功能性缺氧的肌管中，线粒体钙的摄取降低，以响应肌浆网钙的收缩释放。在肌管和人骨骼肌中，线粒体适应性反应和收缩后的重塑均减弱。我们的结果表明，通过调节钙的摄取，线粒体电子转移系统是在功能性缺氧下协调细胞适应的枢纽。
