Tissue-specific seasonal changes in mitochondrial respiratory function and membrane composition in the golden-mantled ground squirrel
Date
2016
Authors
Heim, Ashley, author
Florant, Gregory, advisor
Chicco, Adam, committee member
Mykles, Donald, committee member
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Abstract
Mammals that hibernate, such as the golden-mantled ground squirrel (Callospermophilus lateralis; GMGS), cease to feed, reduce metabolic rate, and lower body temperature (Tb) during the winter months, surviving almost exclusively on the oxidation of lipids from endogenous fat stores. Whether mitochondria, the cellular sites of oxidative metabolism, undergo changes in response to low Tb, hypometabolism, and decreasing ambient temperature (Ta) to facilitate this remarkable phenotype is unclear. It has been postulated that changes in mitochondrial membrane composition reported in response to cold exposure in some species may facilitate maintenance of respiratory enzyme function with decreasing Tb. However, no studies to date have investigated the function and membrane fatty acid (FA) composition of mitochondria from different tissues across seasons in a hibernating mammal. We hypothesize that tissue-specific differences in mitochondrial respiration occur across seasons in the GMGS that may parallel distinct changes in mitochondrial membrane composition. We compared the respiration, substrate preference, and membrane composition of GMGS mitochondria isolated from liver, heart, skeletal muscle, and brown adipose tissue (BAT) from summer, fall (prehibernating), winter (hibernating), and spring (posthibernating) seasons. Maximal mitochondrial oxidative phosphorylation (OXPHOS)-supported respiration was determined by high-resolution respirometry at 37ᵒC in the presence of saturating concentrations of ADP and respiratory substrates. Mitochondrial membrane FA composition was determined by gas chromatography on phospholipid fractions obtained from isolated mitochondria. Maximal OXPHOS assayed at 37ᵒC tended to increase from summer to winter in liver, heart and BAT, and decrease in skeletal muscle, with tissue- and season-specific changes in pyruvate versus FA (palmitoylcarnitine) oxidation capacity. OXPHOS capacity was uniformly suppressed by decreasing Ta in all tissue mitochondria from torpid GMGS in the winter, despite widely variable changes in mitochondrial membrane composition across tissues and seasons. Taken together, these findings argue against a consistent relationship between changes in mitochondrial membrane composition and respiratory function across seasons in GMGS, but highlight distinct tissue- and season-specific differences that may have important biological effects that remain to be elucidated.
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Subject
hibernation
OXPHOS
physiology
mitochondria
fatty acids
phospholipids