title: Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan.
abstract: 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.
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Filippo
authors.initials: F
authors.lastname: Scialò
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Sriram
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, and CIBERER, ISCIII, Seville 41013, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernández-Ayala
authors.affiliation: The Institute of Theoretical and Experimental Biophysics RAS, Pushchino 142290, Russia.
authors.forename: Nina
authors.initials: N
authors.lastname: Gubina
authors.affiliation: Department of Biosciences, Åbo Akademi University, Turku FI-20520, Finland.
authors.forename: Madis
authors.initials: M
authors.lastname: Lõhmus
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Glyn
authors.initials: G
authors.lastname: Nelson
authors.affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Logan
authors.affiliation: Department of Biosciences, Åbo Akademi University, Turku FI-20520, Finland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, and CIBERER, ISCIII, Seville 41013, Spain.
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid 28029, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Enríquez
authors.affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address: Alberto.Sanz@newcastle.ac.uk.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanz
mesh_terms: D000375:Aging; D000818:Animals; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism*; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D042967:Electron Transport Complex I
keywords: aging; coenzyme Q; electron transport chain; mitochondria; reactive oxygen species