Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster.

Redox Biology
Filippo ScialòAlberto Sanz

Abstract

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 str...Continue Reading

References

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Oct 29, 2003·Antioxidants & Redox Signaling·Denham Harman
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Apr 15, 2016·Cell Metabolism·Filippo ScialòAlberto Sanz
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Aug 21, 2018·Cell Metabolism·Sukru Anil DoganCarlo Viscomi

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Citations

Jun 6, 2020·Antioxidants·Ryan J Mailloux
Jan 16, 2021·Free Radical Biology & Medicine·Filippo Scialo, Alberto Sanz
Jan 31, 2021·Nature Communications·Zhan YinJudy Hirst
Feb 11, 2021·The Journal of Experimental Biology·Lisa Bjerregaard JørgensenNicolas Pichaud
Nov 4, 2021·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Chidozie N OkoyeCollins Kamunde

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Datasets Mentioned

BETA
E-MTAB-7952
GO0019731

Methods Mentioned

BETA
RNAseq
PCR

Software Mentioned

GraphPad Prism
STAR
Volcano Plot
ArrayExpress
ImageJ

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