Mitochondrial ROS produced via reverse electron transport extend animal lifespan

Filippo Scialò, Ashwin Sriram, Daniel Fernández-Ayala, Nina Gubina, Madis Lohmus, Glyn Nelson, Angela Logan, Helen Cooper, Plácido Navas, Jose Antonio Enríquez, Michael P. Murphy, Alberto Sanz

Research output: Contribution to journalArticleScientificpeer-review

209 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)725–734
Number of pages10
JournalCell Metabolism
Issue number4
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

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