![]() Instead, I shall develop a consensus about how mitochondria produce ROS and indicate current uncertainties and future issues to be addressed. Since then, a huge literature has developed on the sources and consequences of mitochondrial ROS production, which I will not attempt to cover systematically. The parallel discovery that mitochondria contain their own SOD (superoxide dismutase), MnSOD, confirmed the biological significance of mitochondrial O 2 Later, it was confirmed that this H 2O 2 arose from the dismutation of superoxide (O 2 The first report that the respiratory chain produced ROS came in 1966, followed by the pioneering work of Chance and colleagues who showed that isolated mitochondria produce H 2O 2. Consequently, knowledge of how mitochondria produce ROS is vital to understand a range of currently important biomedical topics ( Figure 1). This ROS production contributes to mitochondrial damage in a range of pathologies and is also important in redox signalling from the organelle to the rest of the cell. Mitochondria are an important source of ROS (reactive oxygen species) within most mammalian cells. − and H 2O 2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.There is a clear need to develop better methods to measure mitochondrial O 2 Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. −-production rates by isolated mitochondria, and such extrapolations in the literature are misleading.− generation by mitochondria in vivo from O 2.Consequently, it is not possible to estimate O 2 ![]() − within the mitochondrial matrix depends critically on Δp, the NADH/NAD + and CoQH 2/CoQ ratios and the local O 2 concentration, which are all highly variable and difficult to measure in vivo.For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD + ratio, the extent of O 2 − 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.Two modes of operation by isolated mitochondria result in significant O 2 − is related to the concentration of potential electron donors, the local concentration of O 2 and the second-order rate constants for the reactions between them.− production within the matrix of mammalian mitochondria.−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O 2.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.
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