title: Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels.
abstract: During hibernation, animals cycle between periods of torpor, during which body temperature (T(b)) and metabolic rate (MR) are suppressed for days, and interbout euthermia (IBE), during which T(b) and MR return to resting levels for several hours. In this study, we measured respiration rates, membrane potentials, and reactive oxygen species (ROS) production of liver and skeletal muscle mitochondria isolated from ground squirrels (Ictidomys tridecemlineatus) during torpor and IBE to determine how mitochondrial metabolism is suppressed during torpor and how this suppression affects oxidative stress. In liver and skeletal muscle, state 3 respiration measured at 37°C with succinate was 70% and 30% lower, respectively, during torpor. In liver, this suppression was achieved largely via inhibition of substrate oxidation, likely at succinate dehydrogenase. In both tissues, respiration by torpid mitochondria further declined up to 88% when mitochondria were cooled to 10°C, close to torpid T(b). In liver, this passive thermal effect on respiration rate reflected reduced activity of all components of oxidative phosphorylation (substrate oxidation, phosphorylation, and proton leak). With glutamate + malate and succinate, mitochondrial free radical leak (FRL; proportion of electrons leading to ROS production) was higher in torpor than IBE, but only in liver. With succinate, higher FRL likely resulted from increased reduction state of complex III during torpor. With glutamate + malate, higher FRL resulted from active suppression of complex I ROS production during IBE, which may limit ROS production during arousal. In both tissues, ROS production and FRL declined with temperature, suggesting ROS production is also reduced during torpor by passive thermal effects.
authors: Department of Biology, University of Western Ontario, London, Canada. jbrow67@uwo.ca
authors: Jason C L
authors: JC
authors: Brown
authors: Dillon J
authors: DJ
authors: Chung
authors: Kathleen R
authors: KR
authors: Belgrave
authors: James F
authors: JF
authors: Staples
mesh_terms: D000818:Animals; D005260:Female; D005971:Glutamates / Q000378:metabolism; D006605:Hibernation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008930:Mitochondria, Liver / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012589:Sciuridae / Q000378:metabolism*; D012621:Seasons; D013696:Temperature
chemical_list: D005971:Glutamates; D008293:Malates; D017382:Reactive Oxygen Species