Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster
Filippo Scialò,
Ashwin Sriram,
Rhoda Stefanatos,
Ruth V. Spriggs,
Samantha H.Y. Loh,
L. Miguel Martins,
Alberto Sanz
Affiliations
Filippo Scialò
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom; Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, United Kingdom; Corresponding authors.
Ashwin Sriram
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom
Rhoda Stefanatos
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom
Ruth V. Spriggs
MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, United Kingdom
Samantha H.Y. Loh
MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, United Kingdom
L. Miguel Martins
MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, United Kingdom
Alberto Sanz
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom; Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, United Kingdom; Corresponding authors.
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 H2O2 by overexpressing mitochondrial catalase (mtCAT), reduces survival dramatically in flies under stress. Our results uncover a specific ROS signalling pathway where hydrogen peroxide (H2O2) generated by CI via RET is required to activate adaptive mechanisms, maximising survival under stress conditions.
