Uncoupling to survive? The role of mitochondrial inefficiency in ageing.

TitleUncoupling to survive? The role of mitochondrial inefficiency in ageing.
Publication TypeJournal Article
Year of Publication2000
AuthorsBrand, MD
JournalExp Gerontol
Volume35
Issue6-7
Pagination811-20
Date Published2000 Sep
ISSN0531-5565
KeywordsAging, Animals, Biological Evolution, Humans, Mitochondria, Oxidative Phosphorylation, Proton-Motive Force, Rats, Reactive Oxygen Species
Abstract

Mitochondria are incompletely coupled, and during oxidative phosphorylation some of the redox energy in substrates is lost as heat. Incomplete coupling is mostly due to a natural leak of protons across the mitochondrial inner membrane. In rat hepatocytes the futile cycle of proton pumping and proton leak is responsible for 20-25% of respiration; in perfused rat muscle the value is 35-50%. Mitochondrial proton cycling is estimated to cause 20-25% of basal metabolic rate in rats. Proton cycling is equally prominent in hepatocytes from several different mammalian and ectotherm species, so it may be a general pathway of ecologically significant energy loss in all aerobes. Because it occurs in ectotherms, thermogenesis cannot be its primary function. Instead, an attractive candidate for the function of the universal and expensive energy-dissipating proton cycle is to decrease the production of superoxide and other reactive oxygen species (ROS). This could be important in helping to minimise oxidative damage to DNA and in slowing ageing. Mitochondria are the major source of cellular ROS, and increased mitochondrial proton conductance leads to oxidation of ubiquinone and decreased ROS production in isolated mitochondria. However, to date there is no direct evidence in cells or organisms that mitochondrial proton cycling lowers ROS production or oxidative damage or that it increases lifespan.

DOI10.1016/s0531-5565(00)00135-2
Alternate JournalExp. Gerontol.
Citation Key10.1016/s0531-5565(00)00135-2
PubMed ID11053672