High fatty acid oxidation capacity and phosphorylation control despite elevated leak and reduced respiratory capacity in northern elephant seal muscle mitochondria

Abstract

Northern elephant seals (Mirounga angustirostris) are extreme, hypoxia-adapted endotherms that rely largely on aerobic metabolism during extended breath-hold dives in near-freezing water temperatures. While many aspects of their physiology have been characterized to account for these remarkable feats, the contribution of adaptations in the aerobic powerhouses of muscle cells, the mitochondria, are unknown. In the present study, the ontogeny and comparative physiology of elephant seal muscle mitochondrial respiratory function was investigated under a variety of substrate conditions and respiratory states. Intact mitochondrial networks were studied by high-resolution respirometry in saponin-permeabilized fiber bundles obtained from primary swimming muscles of pup, juvenile and adult seals, and compared with fibers from adult human vastus lateralis. Results indicate that seal muscle maintains a high capacity for fatty acid oxidation despite a progressive decrease in total respiratory capacity as animals mature from pups to adults. This is explained by a progressive increase in phosphorylation control and fatty acid utilization over pyruvate in adult seals compared with humans and seal pups. Interestingly, despite higher indices of oxidative phosphorylation efficiency, juvenile and adult seals also exhibit a ~50% greater capacity for respiratory 'leak' compared with humans and seal pups. The ontogeny of this phenotype suggests it is an adaptation of muscle to the prolonged breath-hold exercise and highly variable ambient temperatures experienced by mature elephant seals. These studies highlight the remarkable plasticity of mammalian mitochondria to meet the demands for both efficient ATP production and endothermy in a cold, oxygen-limited environment.

Development of endothermy and concomitant increases in cardiac and skeletal muscle mitochondrial respiration in the precocial Pekin duck (Anas platyrhynchos domestica)

“…OXPHOS CI+CII capacity in penguin chicks was significantly lower than that of adults and those measured in our study animals. Our measured levels of OXPHOS CI+CII capacity in the duck thigh muscle were similar to levels measured in human vastus lateralis muscles (Chicco et al, 2014). Other studies examining metabolic enzyme development in skeletal muscles have revealed similar developmental trends as those shown here (e.g.…”

Development of Dive Capacity in Northern Elephant Seals (Mirounga angustirostris): Reduced Body Reserves at Weaning Are Associated with Elevated Body Oxygen Stores during the Postweaning Fast

“…These data are congruent with previous reports of declining resting and submerged metabolic rates during the PWF (Rea and Costa 1992;Tift et al 2013), with a decrease in plasma LDH activity during the first 5 wk of fasting (Tavoni et al 2013), and with stable mitochondrial fat oxidation capacity during an ontogenetic decline in mitochondrial respiratory capacity in swimming muscle (Chicco et al 2014). The decrease in aerobic enzyme activities observed in this study may be an important component of development that underlies the low diving metabolic rates this species exhibits while foraging at sea (Maresh et al 2014).…”

“…In addition to large body oxygen stores, deep divers also exhibit reduced metabolic capacity in swimming muscles relative to athletic terrestrial mammals, which may enable maintenance of aerobic metabolism at a reduced level while diving (Reed et al 1994;Kanatous et al 2002;Chicco et al 2014). Juveniles of most phocids are not sufficiently developed at weaning to forage successfully and must undergo a developmental period to attain sufficient physiological capacity to support foraging (Thorson and LeBoeuf 1994;Noren et al 2003Noren et al , 2005.…”

Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques

“…Any samples showing a greater than 10% increase in respiratory flux under near-maximal OXPHOS states were excluded from the study. Muscles were dissected in ice-cold BIOPS and teased fiber bundles (5-8 mg) were permeabilized in BIOPS with 30 μg/ml saponin for 20 minutes, washed, and weighed as described (74). Mitochondrial respiratory function was measured in PMFBs by high-resolution respirometry using an Oxygraph-2K system (Oroboros Instruments).…”

“…All respirometry data were collected at 37°C in a hyperoxygenated environment (250-400 μM O 2 ) to avoid potential oxygen diffusion limitations in PMFBs (75). Two titration protocols were run in parallel to measure mitochondrial function as previously described (74). For protocol 1, sequential additions of 5 mM pyruvate and 2 mM malate, 4 mM ADP, 10 mM glutamate, 10 mM succinate, 10 μM cytochrome c, 2 μg/ml oligomycin, followed by addition of the uncoupling agent carbonylcyanide p-trifluoromethoxy-phenylhydrazone (FCCP) in 0.5-μM steps, to each chamber.…”