Mitochondrial ROS signalling requires uninterrupted electron flow and is lost during ageing in flies

Graham, C. et al. (2022) Mitochondrial ROS signalling requires uninterrupted electron flow and is lost during ageing in flies. GeroScience, 44(4), pp. 1961-1974. (doi: 10.1007/s11357-022-00555-x) (PMID:35355221) (PMCID:PMC9616974)

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Mitochondrial reactive oxygen species (mtROS) are cellular messengers essential for cellular homeostasis. In response to stress, reverse electron transport (RET) through respiratory complex I generates high levels of mtROS. Suppression of ROS production via RET (ROS-RET) reduces survival under stress, while activation of ROS-RET extends lifespan in basal conditions. Here, we demonstrate that ROS-RET signalling requires increased electron entry and uninterrupted electron flow through the electron transport chain (ETC). We find that in old fruit flies, ROS-RET is abolished when electron flux is decreased and that their mitochondria produce consistently high levels of mtROS. Finally, we demonstrate that in young flies, limiting electron exit, but not entry, from the ETC phenocopies mtROS generation observed in old individuals. Our results elucidate the mechanism by which ROS signalling is lost during ageing.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Zhang, Mr Tong and Scialo, Dr Filippo and Sanz Montero, Professor Alberto and Huerta Uribe, Mr Alejandro and Maddocks, Professor Oliver and Stefanatos, Dr Rhoda
Authors: Graham, C., Stefanatos, R., Yek, A. E.H., Spriggs, R. V., Loh, S. H.Y., Huerta Uribe, A., Zhang, T., Martins, L. M., Maddocks, O. D.K., Scialo, F., and Sanz, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:GeroScience
ISSN (Online):2509-2723
Published Online:30 March 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in GeroScience 44(4): 1961-1974
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
311154Rate of AutophagyAlberto Sanz MonteroBiotechnology and Biological Sciences Research Council (BBSRC)BB/R008167/2Institute of Molecular, Cell & Systems Biology
310196Senior Research Fellowship, `ROS via RET: a redox regulated pathway to extend lifespanAlberto Sanz MonteroWellcome Trust (WELLCOTR)212241/A/18/ZInstitute of Molecular, Cell & Systems Biology
171982Targeting Tumour Metabolism for Cancer Therapy and Diagnosis.Oliver MaddocksCancer Research UK (CRUK)C53309/A19702Institute of Cancer Sciences