Reactive oxygen species generation by reverse electron transfer at mitochondrial complex I under simulated early reperfusion conditions.

Autor:	Tabata Fukushima C; Departments of Anesthesiology, University of Rochester Medical Center, USA; Departments of Biochemistry, University of Rochester Medical Center, USA; Pharmacology and Physiology, University of Rochester Medical Center, USA., Dancil IS; Departments of Anesthesiology, University of Rochester Medical Center, USA., Clary H; Departments of Biochemistry, University of Rochester Medical Center, USA., Shah N; Pharmacology and Physiology, University of Rochester Medical Center, USA., Nadtochiy SM; Departments of Anesthesiology, University of Rochester Medical Center, USA., Brookes PS; Departments of Anesthesiology, University of Rochester Medical Center, USA; Pharmacology and Physiology, University of Rochester Medical Center, USA. Electronic address: paul_brookes@urmc.rochester.edu.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2024 Apr; Vol. 70, pp. 103047. Date of Electronic Publication: 2024 Jan 27.
DOI:	10.1016/j.redox.2024.103047
Abstrakt:	Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90 % of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury. However, numerous factors present in early reperfusion may impact Cx-I RET, including: (i) High [NADH]; (ii) High [lactate]; (iii) Mildly acidic pH; (iv) Defined ATP/ADP ratios; (v) Presence of the nucleosides adenosine and inosine; and (vi) Defined free [Ca 2+ ]. Herein, experiments with mouse cardiac mitochondria revealed that under simulated early reperfusion conditions including these factors, total mitochondrial ROS generation was only 56 ± 17 % of that seen with succinate alone (mean ± 95 % confidence intervals). Of this ROS, only 52 ± 20 % was assignable to Cx-I RET. A further 14 ± 7 % could be assigned to complex III, with the remainder (34 ± 11 %) likely originating from other ROS sources upstream of the Cx-I Q site. Together, these data suggest the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and other ROS sources may contribute a significant fraction of ROS in early reperfusion. Competing Interests: Declaration of competing interest The authors hereby state that they have no conflicts of interest, financial or otherwise, regarding the content of this paper. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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