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)

Abstract

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
• Status: Published
• Refereed: Yes
• 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
• Publisher: Springer
• ISSN: 2509-2715
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
311154		Rate of Autophagy	Alberto Sanz Montero	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/R008167/2	Institute of Molecular, Cell & Systems Biology
310196		Senior Research Fellowship, `ROS via RET: a redox regulated pathway to extend lifespan	Alberto Sanz Montero	Wellcome Trust (WELLCOTR)	212241/A/18/Z	Institute of Molecular, Cell & Systems Biology
171982		Targeting Tumour Metabolism for Cancer Therapy and Diagnosis.	Oliver Maddocks	Cancer Research UK (CRUK)	C53309/A19702	Institute of Cancer Sciences