ROS via RET: a redox regulated pathway to extend lifespan (360G-Wellcome-212241_Z_18_Z)
Reactive Oxygen Species (ROS) play a dual role in cellular physiology. On one hand, ROS are damaging oxidants that have been proposed to cause ageing. On the other, ROS are essential messengers required for maintaining cellular homeostasis. The aged and sick accumulate defective mitochondria that generate high levels of ROS, but antioxidant therapies fail to improve prognosis or extend lifespan. Furthermore, increasing mitochondrial ROS levels in animals extends lifespan rather than reducing it. A new paradigm explains these contradictory results proposing that under normal physiological conditions, ROS are only produced at specific sites (e.g. mitochondria) by specific ROS generators (e.g. respiratory complex I) which regulate distinct redox signalling pathways. Conversely under pathological conditions ROS are produced at unspecific places causing oxidative stress. My laboratory has characterized the first site-specific ROS signalling pathway which regulates animal lifespan: ROS produced via reverse electron transport (RET) at respiratory complex I. This proposal will fully characterize this new redox signalling pathway by addressing three aims: (i) identify the genes and proteins involved in the initiation, amplification and neutralization of ROS-RET, (ii) understand when and where ROS-RET needs to be activated to extend lifespan, and (iii) dissect the pathological consequences of dysregulation of ROS-RET signalling.
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Grant Details
Amount Awarded | 1512586 |
Applicant Surname | Sanz |
Approval Committee | Science Interview Panel |
Award Date | 2018-07-17T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Senior Research Fellowship Basic |
Internal ID | 212241/Z/18/Z |
Lead Applicant | Prof Alberto Sanz |
Partnership Value | 1512586 |
Planned Dates: End Date | 2020-01-05T00:00:00+00:00 |
Planned Dates: Start Date | 2019-05-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | North East |
Sponsor(s) | Prof Robert Lightowlers |