Szibor 2019 Biochim Biophys Acta Bioenerg: Difference between revisions
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{{Publication | {{Publication | ||
|title=Szibor M, Gainutdinov T, Fernandez-Vizarra E, Dufour E, Gizatullina Z, Debska-Vielhaber G, Heidler J, Wittig I, Viscomi C, Gellerich F, Moore AL (2019) Bioenergetic consequences from xenotopic expression of a tunicate AOX in mouse mitochondria: | |title=Szibor M, Gainutdinov T, Fernandez-Vizarra E, Dufour E, Gizatullina Z, Debska-Vielhaber G, Heidler J, Wittig I, Viscomi C, Gellerich F, Moore AL (2019) Bioenergetic consequences from xenotopic expression of a tunicate AOX in mouse mitochondria: switch from RET and ROS to FET. Biochim Biophys Acta Bioenerg 1861:148137. | ||
|info=[https://www.ncbi.nlm.nih.gov/pubmed/31825809 PMID: 31825809 Open Access] | |info=[https://www.ncbi.nlm.nih.gov/pubmed/31825809 PMID: 31825809 Open Access] | ||
|authors=Szibor M, Gainutdinov T, Fernandez-Vizarra E, Dufour E, Gizatullina Z, Debska-Vielhaber G, Heidler J, Wittig I, Viscomi C, Gellerich F, Moore | |authors=Szibor M, Gainutdinov T, Fernandez-Vizarra E, Dufour E, Gizatullina Z, Debska-Vielhaber G, Heidler J, Wittig I, Viscomi C, Gellerich F, Moore Anthony L | ||
|year=2019 | |year=2019 | ||
|journal=Biochim Biophys Acta Bioenerg | |journal=Biochim Biophys Acta Bioenerg | ||
|abstract=Electron transfer from all respiratory | |abstract=Electron transfer from all respiratory system dehydrogenases of the electron transport system (ETS) converges at the level of the quinone (Q) pool. The Q redox state is thus a function of electron input (reduction) and output (oxidation) and closely reflects the mitochondrial respiratory state. Disruption of electron flux at the level of the cytochrome bc<sub>1</sub> Complex (CIII) or cytochrome c oxidase (CIV) shifts the Q redox poise to a more reduced state which is generally sensed as respiratory stress. To cope with respiratory stress, many species, but not insects and vertebrates, express alternative oxidase (AOX) which acts as an electron sink for reduced Q and by-passes CIII and CIV. Here, we used ''Ciona intestinalis'' AOX xenotopically expressed in mouse mitochondria to study how respiratory states impact the Q poise and how AOX may be used to restore respiration. Particularly interesting is our finding that electron input through succinate dehydrogenase (CII), but not NADH:ubiquinone oxidoreductase (CI), reduces the Q pool almost entirely (>90 %) irrespective of the respiratory state. AOX enhances the forward electron transfer (FET) from CII thereby decreasing reverse electron transfer (RET) and ROS specifically when non-phosphorylating. AOX is not engaged with CI substrates, however, unless a respiratory inhibitor is added. This sheds new light on Q poise signaling, the biological role of CII which enigmatically is the only ETS complex absent from respiratory supercomplexes but yet participates in the tricarboxylic acid (TCA) cycle. Finally, we delineate potential risks and benefits arising from therapeutic AOX transfer. | ||
<small>Copyright ยฉ 2019 The Authors. Published by Elsevier B.V. All rights reserved.</small> | <small>Copyright ยฉ 2019 The Authors. Published by Elsevier B.V. All rights reserved.</small> | ||
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|pathways=N, S, NS, ROX | |pathways=N, S, NS, ROX | ||
|instruments=Oxygraph-2k, O2k-Fluorometer | |instruments=Oxygraph-2k, O2k-Fluorometer | ||
|additional=Labels, 2020-01, | |additional=Labels, 2020-01, AmR, AOX, Q, | ||
}} | }} |
Revision as of 12:08, 7 March 2020
Szibor M, Gainutdinov T, Fernandez-Vizarra E, Dufour E, Gizatullina Z, Debska-Vielhaber G, Heidler J, Wittig I, Viscomi C, Gellerich F, Moore AL (2019) Bioenergetic consequences from xenotopic expression of a tunicate AOX in mouse mitochondria: switch from RET and ROS to FET. Biochim Biophys Acta Bioenerg 1861:148137. |
Szibor M, Gainutdinov T, Fernandez-Vizarra E, Dufour E, Gizatullina Z, Debska-Vielhaber G, Heidler J, Wittig I, Viscomi C, Gellerich F, Moore Anthony L (2019) Biochim Biophys Acta Bioenerg
Abstract: Electron transfer from all respiratory system dehydrogenases of the electron transport system (ETS) converges at the level of the quinone (Q) pool. The Q redox state is thus a function of electron input (reduction) and output (oxidation) and closely reflects the mitochondrial respiratory state. Disruption of electron flux at the level of the cytochrome bc1 Complex (CIII) or cytochrome c oxidase (CIV) shifts the Q redox poise to a more reduced state which is generally sensed as respiratory stress. To cope with respiratory stress, many species, but not insects and vertebrates, express alternative oxidase (AOX) which acts as an electron sink for reduced Q and by-passes CIII and CIV. Here, we used Ciona intestinalis AOX xenotopically expressed in mouse mitochondria to study how respiratory states impact the Q poise and how AOX may be used to restore respiration. Particularly interesting is our finding that electron input through succinate dehydrogenase (CII), but not NADH:ubiquinone oxidoreductase (CI), reduces the Q pool almost entirely (>90 %) irrespective of the respiratory state. AOX enhances the forward electron transfer (FET) from CII thereby decreasing reverse electron transfer (RET) and ROS specifically when non-phosphorylating. AOX is not engaged with CI substrates, however, unless a respiratory inhibitor is added. This sheds new light on Q poise signaling, the biological role of CII which enigmatically is the only ETS complex absent from respiratory supercomplexes but yet participates in the tricarboxylic acid (TCA) cycle. Finally, we delineate potential risks and benefits arising from therapeutic AOX transfer.
Copyright ยฉ 2019 The Authors. Published by Elsevier B.V. All rights reserved. โข Keywords: Alternative oxidase (AOX), Mitochondria, OXPHOS, Quinone pool, ROS, Xenotopic expression โข Bioblast editor: Plangger M โข O2k-Network Lab: FI Helsinki Jacobs HT, DE Magdeburg Gellerich FN, FI Tampere Dufour E, DE Magdeburg Debska-Vielhaber G, DE Frankfurt Wittig I, UK Brighton Moore AL
Labels: MiParea: Respiration
Organism: Mouse
Tissue;cell: Heart
Preparation: Isolated mitochondria
Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Supercomplex, TCA cycle and matrix dehydrogenases
Regulation: Redox state
Coupling state: LEAK, OXPHOS, ET
Pathway: N, S, NS, ROX
HRR: Oxygraph-2k, O2k-Fluorometer
Labels, 2020-01, AmR, AOX, Q