title: Examining the mechanisms responsible for lower ROS release rates in liver mitochondria from the long-lived house sparrow (Passer domesticus) and big brown bat (Eptesicus fuscus) compared to the short-lived mouse (Mus musculus).
abstract: Lower ROS release rate in long-lived species is likely caused by decreased reduction of electron transport chain (ETC) complexes, but how this is achieved remains largely unknown. We compared liver mitochondrial H(2)O(2) release rates among endotherms of comparable size and metabolic rate: house sparrow and big brown bat (both long-lived) and house mouse (short-lived). We hypothesized that low ROS release rates in long-lived species result from (i) lower mitochondrial respiration rate, (ii) increased mitochondrial proton conductance ('uncoupling to survive'), and/or (iii) increased ETC oxidative capacity ('spare oxidative capacity'). H(2)O(2) release rate was 70% lower in bats than mice despite similar respiration rates. Consistent with 'uncoupling to survive', proton leakiness was 3-fold higher in bats at membrane potentials above 130mV. Basal H(2)O(2) release rate and respiration rates were 2-fold higher in sparrows than mice. Consistent with 'spare oxidative capacity', subsaturating succinate decreased H(2)O(2) release rate in sparrows but not mice. Moreover, succinate:Cytochrome c oxidoreductase activity was 3-fold higher in sparrows, and ETC inhibitors increased ROS release rate 20-27-fold in sparrows (with glutamate or subsaturating succinate) but only 4-5-fold in mice. Taken together these data suggest that complexes I and III are less reduced under physiological conditions in sparrows. We conclude that different long-lived species may use distinct mechanisms to lower mitochondrial ROS release rate.
authors.affiliation: Department of Biology, University of Western Ontario, ON, Canada. jbrow63@uwo.ca
authors.forename: Jason C L
authors.initials: JC
authors.lastname: Brown
authors.forename: Grant B
authors.initials: GB
authors.lastname: McClelland
authors.forename: Paul A
authors.initials: PA
authors.lastname: Faure
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Klaiman
authors.forename: James F
authors.initials: JF
authors.lastname: Staples
mesh_terms: D000375:Aging; D000818:Animals; D002685:Chiroptera; D045304:Cytochromes c; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008136:Longevity; D008564:Membrane Potentials; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism*; D008938:Mitosis; D010088:Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species; D046370:Sparrows; D019802:Succinic Acid / Q000737:chemistry
chemical_list: D017382:Reactive Oxygen Species; D045304:Cytochromes c; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D010088:Oxidoreductases