Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
Faculty of Medical Sciences, Wellcome Centre for Mitochondrial Research, Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
Geroscience. 2022 Aug;44(4):1961-1974. doi: 10.1007/s11357-022-00555-x. Epub 2022 Mar 30.
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.
线粒体活性氧（mtROS）是细胞内稳态所必需的细胞信使。在应激反应中，通过呼吸复合物 I 的逆向电子传递（RET）会产生高水平的 mtROS。通过 RET 抑制 ROS 生成（ROS-RET）会降低应激下的存活率，而激活 ROS-RET 则会延长基础条件下的寿命。在这里，我们证明了 ROS-RET 信号需要增加电子进入和电子传递链（ETC）中不间断的电子流。我们发现，在老年果蝇中，当电子通量减少时，ROS-RET 被废除，并且它们的线粒体持续产生高水平的 mtROS。最后，我们证明在年轻的果蝇中，限制 ETC 中电子的出口，而不是进入，会模拟老年个体中观察到的 mtROS 生成。我们的结果阐明了 ROS 信号在衰老过程中丢失的机制。
