Metabolic depression and enhanced O(2) affinity of mitochondria in hypoxic hypometabolism

This study examined whether the steady-state hypometabolism seen in overwintering frogs (Rana temporaria) is reflected at the mitochondrial level either by a reduction in their resting (state 4) and active (state 3) respiration rates and/or by increases in O(2) affinity. We isolated mitochondria from the skeletal muscle of cold-submerged frogs at different stages during their hibernation in normoxic and hypoxic water. A modest metabolic depression at the whole animal level (normoxic submergence) was not associated with a reduction in mitochondrial state 4 and state 3 respiration rates. However, mitochondria isolated from frogs that were submerged for 1 mo manifested an increase in their O(2) affinity compared with controls and with animals submerged for 4 mo. Hypometabolism was more pronounced at the whole animal level during hypoxic submergence and was accompanied by 1) a reduction in mitochondrial state 4 and state 3 rates and 2) an increase in the O(2) affinity of mitochondria. These findings demonstrate that metabolic depression can be reflected at all levels of biological organization in hypoxia-tolerant animals.