Tissue‐Specific Seasonal Changes in Mitochondrial Membrane Composition and Respiratory Function in the Golden‐Mantled Ground Squirrel

Abstract

Mammals that hibernate, such as the golden‐mantled ground squirrel (Callospermophilus lateralis; GMGS), cease to feed, reduce metabolic rate, and lower body temperature 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 adaptive changes in response to hypometabolism and decreasing ambient temperature 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 temperature. However, no studies to date have investigated the function and membrane fatty acid composition of mitochondria from different tissues from the warm summer months, to fall and winter in a hibernator. 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 respiratory capacity, oxidative enzyme activity, and membrane composition of GMGS mitochondria isolated from liver, heart, skeletal muscle, and brown adipose tissue (BAT) from summer, fall, and winter (torpid) seasons. Maximal mitochondrial oxidative phosphorylation (OXPHOS)‐supported respiration was determined by high‐resolution respirometry at 37°C, 25°C, and 15°C in the presence of saturating concentrations of ADP and respiratory substrates. Mitochondrial membrane fatty acid composition was determined by gas chromatography on phospholipid fractions obtained from isolated mitochondria. Maximal OXPHOS assayed at 37°C 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 fatty acid (palmitoylcarnitine) oxidation capacity. OXPHOS capacity was uniformly suppressed by decreasing assay temperature in all tissue mitochondria from torpid GMGS in the winter, despite widely variable changes in mitochondrial membrane composition across tissues and seasons. Interestingly, a consistent relative decrease in mitochondrial membrane docosahexaenoic acid (DHA; 22:6n3) was seen from summer to winter in all tissues, the biological relevance of which merits further investigation. 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.