Hoffman 2009 J Biol Chem: Difference between revisions
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{{Publication | {{Publication | ||
|title=Hoffman DL, Brookes PS | |title=Hoffman DL, Brookes PS (2009) Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions. J Biol Chem 284:16236-45. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/19366681 PMID: 19366681 Open Access] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19366681 PMID: 19366681 Open Access] | ||
|authors=Hoffman DL, Brookes PS | |authors=Hoffman DL, Brookes PS | ||
|year=2009 | |year=2009 | ||
|journal=J Biol Chem | |journal=J Biol Chem | ||
|abstract=The mitochondrial generation of reactive oxygen species (ROS) plays a central role in many cell signaling pathways, but debate still surrounds its regulation by factors, such as substrate availability, [ | |abstract=The mitochondrial generation of reactive oxygen species (ROS) plays a central role in many cell signaling pathways, but debate still surrounds its regulation by factors, such as substrate availability, [O<sub>2</sub>] and metabolic state. Previously, we showed that in isolated mitochondria respiring on succinate, ROS generation was a hyperbolic function of [O<sub>2</sub>]. In the current study, we used a wide variety of substrates and inhibitors to probe the O<sub>2</sub> sensitivity of mitochondrial ROS generation under different metabolic conditions. From such data, the apparent ''K''<sub>''m''</sub> for O<sub>2</sub> of putative ROS-generating sites within mitochondria was estimated as follows: 0.2, 0.9, 2.0, and 5.0 microM O<sub>2</sub> for the complex I flavin site, complex I electron backflow, complex III QO site, and electron transfer flavoprotein quinone oxidoreductase of beta-oxidation, respectively. Differential effects of respiratory inhibitors on ROS generation were also observed at varying [O<sub>2</sub>]. Based on these data, we hypothesize that at physiological [O<sub>2</sub>], complex I is a significant source of ROS, whereas the electron transfer flavoprotein quinone oxidoreductase may only contribute to ROS generation at very high [O<sub>2</sub>]. Furthermore, we suggest that previous discrepancies in the assignment of effects of inhibitors on ROS may be due to differences in experimental [O<sub>2</sub>]. Finally, the data set (see supplemental material) may be useful in the mathematical modeling of mitochondrial metabolism. | ||
}} | }} | ||
== Cited by == | |||
{{Template:Cited by Komlodi 2021 MitoFit AmR}} | |||
{{Template:Cited by Komlodi 2022 MitoFit ROS review}} | |||
{{Labeling | {{Labeling | ||
| | |area=Respiration | ||
|injuries= | |injuries=Oxidative stress;RONS | ||
|organism=Rat | |organism=Rat | ||
|preparations=Isolated | |preparations=Isolated mitochondria | ||
|enzymes=Complex I, Complex III, TCA cycle and matrix dehydrogenases | |||
|topics=Oxygen kinetics, Redox state | |||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
| | |additional=MitoFit 2021 AmR, MitoFit 2022 ROS review | ||
}} | }} |
Latest revision as of 21:38, 13 April 2022
Hoffman DL, Brookes PS (2009) Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions. J Biol Chem 284:16236-45. |
Hoffman DL, Brookes PS (2009) J Biol Chem
Abstract: The mitochondrial generation of reactive oxygen species (ROS) plays a central role in many cell signaling pathways, but debate still surrounds its regulation by factors, such as substrate availability, [O2] and metabolic state. Previously, we showed that in isolated mitochondria respiring on succinate, ROS generation was a hyperbolic function of [O2]. In the current study, we used a wide variety of substrates and inhibitors to probe the O2 sensitivity of mitochondrial ROS generation under different metabolic conditions. From such data, the apparent Km for O2 of putative ROS-generating sites within mitochondria was estimated as follows: 0.2, 0.9, 2.0, and 5.0 microM O2 for the complex I flavin site, complex I electron backflow, complex III QO site, and electron transfer flavoprotein quinone oxidoreductase of beta-oxidation, respectively. Differential effects of respiratory inhibitors on ROS generation were also observed at varying [O2]. Based on these data, we hypothesize that at physiological [O2], complex I is a significant source of ROS, whereas the electron transfer flavoprotein quinone oxidoreductase may only contribute to ROS generation at very high [O2]. Furthermore, we suggest that previous discrepancies in the assignment of effects of inhibitors on ROS may be due to differences in experimental [O2]. Finally, the data set (see supplemental material) may be useful in the mathematical modeling of mitochondrial metabolism.
Cited by
- 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).
- Komlรณdi T, Gnaiger E (2022) Discrepancy on oxygen dependence of mitochondrial ROS production - review. MitoFit Preprints 2022 (in prep).
Labels: MiParea: Respiration
Stress:Oxidative stress;RONS Organism: Rat
Preparation: Isolated mitochondria Enzyme: Complex I, Complex III, TCA cycle and matrix dehydrogenases Regulation: Oxygen kinetics, Redox state Coupling state: OXPHOS
MitoFit 2021 AmR, MitoFit 2022 ROS review