Regulation of succinate-fuelled mitochondrial respiration in liver and skeletal muscle of hibernating thirteen-lined ground squirrels.
Hibernating ground squirrels (Ictidomys tridecemlineatus) alternate between two distinct metabolic states throughout winter: torpor, during which metabolic rate (MR) and body temperature (Tb) are considerably suppressed, and interbout euthermia (IBE), during which MR and Tb briefly return to euthermic levels. Previous studies showed suppression of succinate-fuelled respiration during torpor in liver and skeletal muscle mitochondria; however, these studies used only a single, saturating succinate concentration. Therefore, they could not address whether mitochondrial metabolic suppression occurs under physiological substrate concentrations or whether differences in the kinetics of mitochondrial responses to changing substrate concentration might also contribute to mitochondrial metabolic regulation during torpor. The present study confirmed that succinate oxidation is reduced during torpor in liver and skeletal muscle at 37 and 10°C over a 100-fold range of succinate concentrations. At 37°C, this suppression resulted from inhibition of succinate dehydrogenase (SDH), which had a greater affinity for oxaloacetate (an SDH inhibitor) during torpor. At 10°C, SDH was not inhibited, suggesting that SDH inhibition initiates but does not maintain mitochondrial suppression during torpor. Moreover, in both liver and skeletal muscle, mitochondria from torpid animals maintained relatively higher respiration rates at low succinate concentrations, which reduces the extent of energy savings that can be achieved during torpor, but may also maintain mitochondrial oxidative capacity above some lower critical threshold, thereby preventing cellular and/or mitochondrial injury during torpor and facilitating rapid recruitment of oxidative capacity during arousal.
Department of Biology, University of Western Ontario, London, ON, Canada, N6A 5B7. jbrow63@alumni.uwo.ca
Jason C L
JC
Brown
Dillon J
DJ
Chung
Alex N
AN
Cooper
James F
JF
Staples
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D005260:Female; D006605:Hibernation / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D062907:Oxaloacetic Acid / Q000378:metabolism; D012589:Sciuridae / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism* / Q000494:pharmacology; D013696:Temperature
D062907:Oxaloacetic Acid; D019802:Succinic Acid; D013385:Succinate Dehydrogenase