Abstract
Mitochondrial Reactive Oxygen Species (mtROS) are cellular messengers essential for cellular homeostasis. In response to stress, reverse electron transport (RET) by respiratory complex I generates high levels of mtROS. Suppression of ROS produced 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 found that ROS-RET is abolished in old fruit flies where electron flux is reduced. Instead, mitochondria in aged flies produce consistently high levels of mtROS. Finally, we demonstrate that in young flies reduction of electron exit from the ETC, but not electron entry, phenocopies mtROS generation observed in old individuals. Our results define the mechanism by which ROS signalling is lost during ageing.
Highlights
ROS-RET signalling requires an uninterrupted flow of electrons through the ETC.
ROS-RET signalling fails during ageing, with mitochondria producing persistently high levels of ROS.
Interruption of ROS-RET signalling compromises stress adaptation in old flies.
Reducing electron exit suppresses ROS-RET signalling and phenocopies ROS production observed in old mitochondria.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵$ Share senior authorship.
Abbreviations
- H2O2
- hydrogen peroxide
- CI
- complex I
- CII
- complex II
- CIII
- complex III
- CIV
- complex IV
- CoQ
- coenzyme-Q
- CYA
- Cyanide
- ETC
- electron transport chain
- PPP
- Pentose Phosphate Pathway
- pmf
- proton motive force
- RET
- reverse electron transport
- mtROS
- mitochondrial Reactive Oxygen Species
- ROS-RET
- ROS produced via Reverse Electron Transport
- ROT
- rotenone
- TS
- thermal stress.
