Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster

Scialò, F., Sriram, A., Stefanatos, R. , Spriggs, R. V., Loh, S. H.Y., Martins, L. M. and Sanz, A. (2020) Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster. Redox Biology, 32, 101450. (doi: 10.1016/j.redox.2020.101450) (PMID:32146156) (PMCID:PMC7264463)

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Reactive Oxygen Species (ROS) are essential cellular messengers required for cellular homeostasis and regulate the lifespan of several animal species. The main site of ROS production is the mitochondrion, and within it, respiratory complex I (CI) is the main ROS generator. ROS produced by CI trigger several physiological responses that are essential for the survival of neurons, cardiomyocytes and macrophages. Here, we show that CI produces ROS when electrons flow in either the forward (Forward Electron Transport, FET) or reverse direction (Reverse Electron Transport, RET). We demonstrate that ROS production via RET (ROS-RET) is activated under thermal stress conditions and that interruption of ROS-RET production, through ectopic expression of the alternative oxidase AOX, attenuates the activation of pro-survival pathways in response to stress. Accordingly, we find that both suppressing ROS-RET signalling or decreasing levels of mitochondrial H O by overexpressing mitochondrial catalase (mtCAT), reduces survival dramatically in flies under stress. Our results uncover a specific ROS signalling pathway where hydrogen peroxide (H O ) generated by CI via RET is required to activate adaptive mechanisms, maximising survival under stress conditions.

Item Type:Articles
Additional Information:This study was supported by the European Research Council (260632-ComplexI&Ageing to A. Sa.), BBSRC (BB/M023311/1 and BB/R008167/1 to A. Sa.) and a Wellcome Senior Research Fellowship (212241/A/18/Z to A. Sa.). R.S is a Sir Henry Wellcome Postdoctoral Fellow funded by Wellcome (204715/Z/16/Z). Work in LMM's laboratory is funded by the UK Medical Research Council, intramural project MC_UU_00025/3 (RG94521).
Keywords:AOX, alternative oxidase, complex I, heat stress, reactive oxygen species, reverse electron transport.
Glasgow Author(s) Enlighten ID:Scialo, Dr Filippo and Sanz Montero, Professor Alberto and Stefanatos, Dr Rhoda
Authors: Scialò, F., Sriram, A., Stefanatos, R., Spriggs, R. V., Loh, S. H.Y., Martins, L. M., and Sanz, A.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Redox Biology
ISSN (Online):2213-2317
Published Online:07 February 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Redox Biology 32: 101450
Publisher Policy:Reproduced under a Creative Commons License

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