How mitochondria produce reactive oxygen species.
How mitochondria produce reactive oxygen species.
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DOI：
10.1042/bj20081386
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Murphy MP
中科院分区：
文献类型：
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作者：
Murphy MP
哺乳动物线粒体产生的ROS（活性氧）是重要的，因为它是许多病理学中氧化损伤的基础，并有助于从细胞器到细胞质和细胞核的逆行氧化还原信号传导。超氧化物（O2·−）是近端线粒体ROS，在本综述中，我概述了哺乳动物线粒体基质内O2·−产生的原理。O2·−的通量与潜在电子供体的浓度、O2的局部浓度以及它们之间反应的二级速率常数有关。分离的线粒体有两种运作模式，导致大量的O2·−产生，主要来自复合物I：（i）当线粒体不产生ATP时，因此具有高Δp（质子动力）和还原的CoQ（辅酶Q）库;（ii）当线粒体基质中存在高NADH/NAD+比率时。对于活跃制造ATP的线粒体，因此具有较低的Δp和NADH/NAD+比率，O2·−的产生程度要低得多。线粒体基质中O2·−的产生主要取决于Δp、NADH/NAD+和CoQH 2/CoQ比率以及局部O2浓度，这些都是高度可变的，难以在体内测量。因此，不可能从分离的线粒体的O2·−-产生速率来估计线粒体在体内的O2·−产生，文献中的这种外推是误导性的。即便如此，这里概述的描述有助于理解有利于线粒体ROS产生的因素。显然需要开发更好的方法来测量体内线粒体O2·−和H2 O2的形成，因为这些值的不确定性阻碍了对线粒体ROS在病理性氧化损伤和氧化还原信号传导中的作用的研究。
The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•− production within the matrix of mammalian mitochondria. The flux of O2•− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2•− production is far lower. The generation of O2•− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•− generation by mitochondria in vivo from O2•−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.