Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster
Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster
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DOI：
10.1016/j.redox.2020.101450
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发表时间：
2020-05-01
期刊：
影响因子：
11.4
通讯作者：
Sanz, Alberto
中科院分区：
文献类型：
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作者：
Scialo, Filippo;Sriram, Ashwin;Sanz, Alberto
活性氧(ROS)是细胞内稳态所必需的细胞信使，调节多种动物的寿命。ROS产生的主要部位是线粒体，其中呼吸复合体I(CI)是主要的ROS生成器。CI产生的ROS可触发多种生理反应，这些反应对神经元、心肌细胞和巨噬细胞的生存至关重要。在这里，我们证明了当电子沿正向(正向电子传输，FET)或反向(反向电子传输，RET)流动时，CI产生ROS。我们证明了通过RET产生ROS(ROS-RET)在热应激条件下被激活，而ROS-RET产生的中断，通过交替氧化酶AOX的异位表达，减弱了促进生存的通路在应激反应中的激活。因此，我们发现，通过过度表达线粒体过氧化氢酶(MtCAT)来抑制ROS-RET信号转导或降低线粒体过氧化氢水平，都能显著降低应激下果蝇的存活率。我们的结果揭示了一条特定的ROS信号通路，其中CI通过RET产生的过氧化氢(H2O2)需要激活适应机制，从而在应激条件下最大化存活。
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.