Mitochondrial ROS produced via reverse electron transport extend animal lifespan

Scialò, F. et al. (2016) Mitochondrial ROS produced via reverse electron transport extend animal lifespan. Cell Metabolism, 23(4), pp. 725-734. (doi: 10.1016/j.cmet.2016.03.009) (PMID:27076081) (PMCID:PMC4835580)

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Increased production of reactive oxygen species (ROS) has long been considered a cause of aging. However, recent studies have implicated ROS as essential secondary messengers. Here we show that the site of ROS production significantly contributes to their apparent dual nature. We report that ROS increase with age as mitochondrial function deteriorates. However, we also demonstrate that increasing ROS production specifically through respiratory complex I reverse electron transport extends Drosophila lifespan. Reverse electron transport rescued pathogenesis induced by severe oxidative stress, highlighting the importance of the site of ROS production in signaling. Furthermore, preventing ubiquinone reduction, through knockdown of PINK1, shortens lifespan and accelerates aging; phenotypes that are rescued by increasing reverse electron transport. These results illustrate that the source of a ROS signal is vital in determining its effects on cellular physiology and establish that manipulation of ubiquinone redox state is a valid strategy to delay aging.

Item Type:Articles
Additional Information:This work was supported by the European Research Council (ERC Starting Grant to A. Sanz), the Academy of Finland (Academy Research Fellowship to A. Sanz and Postdoctoral Research grant to H.M.C), the BBSRC (Responsive mode grant to A. Sanz), the Centre for International Mobility (Postdoctoral fellowship to N.G.), the Medical Research Council (M.P.M), and the Spanish Ministry of Health and the Instituto de Salud Carlos III (FIS PI14-01962 to P.N.).
Glasgow Author(s) Enlighten ID:Sanz Montero, Professor Alberto
Authors: Scialò, F., Sriram, A., Fernández-Ayala, D., Gubina, N., Lõhmus, M., Nelson, G., Logan, A., Cooper, H. M., Navas, P., Enríquez, J. A., Murphy, M. P., and Sanz, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Cell Metabolism
ISSN (Online):1932-7420
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Cell Metabolism 23:725-734
Publisher Policy:Reproduced under a Creative Commons License

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