Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster

Publication date: Available online 7 February 2020Source: Redox BiologyAuthor(s): Filippo Scialo, Ashwin Sriram, Rhoda Stefanatos, Ruth V. Spriggs, Samantha H.Y. Loh, L. Miguel Martins, Alberto SanzAbstractReactive 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 or macrophages. Here, we show that CI produces ROS when electrons flow either in the forward (Forward Electron Transport, FET) or reverse direction (Reverse Electron Transport, RET). We demonstrate that ROS produced via RET (ROS-RET) are activated under thermal stress condition and that interruption of ROS-RET production by ectopic expression of the alternative oxidase AOX attenuates the activation of pro-survival pathways in response to stress. Accordingly, we find that 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.Graphical abstract

Source: Redox Biology - February 8, 2020 Category: Biology Source Type: research