Murphy 2009 Biochem J: Difference between revisions
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|abstract=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 ( | |abstract=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 (O<sub>2</sub><sup>โขโ</sup>) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O<sub>2</sub><sup>โขโ</sup> production within the matrix of mammalian mitochondria. The flux of O<sub>2</sub><sup>โขโ</sup> is related to the concentration of potential electron donors, the local concentration of O<sub>2</sub> and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O<sub>2</sub><sup>โขโ</sup> production, predominantly from Complex I: (i) when the mitochondria are not making ATP and consequently have a high ฮp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD<sup>+</sup> ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower ฮp and NADH/NAD<sup>+</sup> ratio, the extent of O<sub>2</sub><sup>โขโ</sup> production is far lower. The generation of O<sub>2</sub><sup>โขโ</sup> within the mitochondrial matrix depends critically on ฮp, the NADH/NAD<sup>+</sup> and CoQH<sub>2</sub>/CoQ ratios and the local O<sub>2</sub> concentration, which are all highly variable and difficult to measure ''in vivo''. Consequently, it is not possible to estimate O<sub>2</sub><sup>โขโ</sup> generation by mitochondria ''in vivo'' from O<sub>2</sub><sup>โขโ</sup>-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 O<sub>2</sub><sup>โขโ</sup> and H<sub>2</sub>O<sub>2</sub> formation ''in vivo'', as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signaling. | ||
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{{Template:Cited by Komlodi 2021 MitoFit Tissue normoxia}} | {{Template:Cited by Komlodi 2021 MitoFit Tissue normoxia}} | ||
{{Template:Cited by Komlodi 2021 MitoFit AmR}} | {{Template:Cited by Komlodi 2021 MitoFit AmR}} | ||
{{Labeling | {{Labeling | ||
|additional=MitoFit 2021 Tissue normoxia, MitoFit 2021 AmR | |additional=MitoFit 2021 Tissue normoxia, MitoFit 2021 AmR | ||
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Revision as of 07:07, 20 December 2022
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1-13. |
Abstract: 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 (O2โขโ) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2โขโ production within the matrix of mammalian mitochondria. The flux of O2โขโ 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 O2โขโ production, predominantly from Complex I: (i) when the mitochondria are not making ATP and consequently have a high ฮp (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 ฮp and NADH/NAD+ ratio, the extent of O2โขโ production is far lower. The generation of O2โขโ within the mitochondrial matrix depends critically on ฮp, 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 O2โขโ generation by mitochondria in vivo from O2โขโ-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 O2โขโ and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signaling.
Cited by
- Komlodi et al (2022) Hydrogen peroxide production, mitochondrial membrane potential and the coenzyme Q redox state measured at tissue normoxia and experimental hyperoxia in heart mitochondria. MitoFit Preprints 2021 (in prep)
- Komlรณdi T, Schmitt S, Zdrazilova L, Donnelly C, Zischka H, Gnaiger E. Oxygen dependence of hydrogen peroxide production in isolated mitochondria and permeabilized cells. MitoFit Preprints (in prep).
- Komlodi et al (2022) Hydrogen peroxide production, mitochondrial membrane potential and the coenzyme Q redox state measured at tissue normoxia and experimental hyperoxia in heart mitochondria. MitoFit Preprints 2021 (in prep)
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