High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia
High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia
复制标题
DOI：
10.1073/pnas.97.20.11080
复制
发表时间：
2000-09-26
影响因子：
11.1
通讯作者：
Hand, SC
中科院分区：
文献类型：
--
作者：
Gnaiger, E;Méndez, G;Hand, SC
线粒体在组织内的微环境中面临低氧水平；然而，分离的线粒体通常在空气饱和的条件下进行研究，这些条件实际上是高氧的，增加氧化应激，并可能损害线粒体功能。另一方面，在缺氧情况下，呼吸和 ATP 供应受到限制。在这些氧气限制的条件下，氧化磷酸化与耗氧耦合的任何妥协都可能加剧 ATP 消耗，导致代谢失败。为了解决这个问题，我们开发了注氧微量热法和 ADP 注射呼吸测定法来评估限制氧供应时的线粒体功能。尽管在高氧水平下 ADP 限制期间磷酸化效率会下降，但我们在此表明，氧化磷酸化在低氧条件下比在空气饱和条件下更有效，正如在 ATP 合成的相同次最大速率下 ADP 通量与总氧通量的较高比率所表明的那样。在低氧条件下，质子泄漏和非耦合呼吸受到抑制，从而减少维持能量消耗。这表明低细胞内氧水平对于避免氧化应激和保护生物能效率的重要性。
Mitochondria are confronted with low oxygen levels in the microenvironment within tissues; yet, isolated mitochondria are routinely studied under air-saturated conditions that are effectively hyperoxic, increase oxidative stress, and may impair mitochondrial function. Under hypoxia, on the other hand, respiration and ATP supply are restricted. Under these conditions of oxygen limitation, any compromise in the coupling of oxidative phosphorylation to oxygen consumption could accentuate ATP depletion, leading to metabolic failure. To address this issue, we have developed the approach of oxygen-injection microcalorimetry and ADP-injection respirometry for evaluating mitochondrial function at limiting oxygen supply. Whereas phosphorylation efficiency drops during ADP limitation at high oxygen levels, we show here that oxidative phosphorylation is more efficient at low oxygen than at air saturation, as indicated by higher ratios of ADP flux to total oxygen flux at identical submaximal rates of ATP synthesis. At low oxygen, the proton leak and uncoupled respiration are depressed, thus reducing maintenance energy expenditure. This indicates the importance of low intracellular oxygen levels in avoiding oxidative stress and protecting bioenergetic efficiency.