Metabolic depression and enhanced O₂affinity of mitochondria in hypoxic hypometabolism

Abstract

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.

Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs

“…This is in agreement with previous studies on hypoxia-tolerant animals such as hibernating frogs and aestivating snails, which show a strong suppression of F O ,F 1 -ATPase activity during prolonged hypoxia St-Pierre et al, 2000c;Bishop et al, 2002;Boutilier and St-Pierre, 2002). In hypoxia, mitochondrial F O ,F 1 -ATPase acts in the reverse direction and becomes an ATP consumer hydrolyzing ATP to prevent the collapse of Δψ (St-Pierre et al, 2000b).…”

Metabolic Flexibility: Hibernation, Torpor, and Estivation

“…While enhanced affinity of mitochondria for O 2 might help to maintain ATP supply in hypoxia (263), overall these results suggest that demand for energy is suppressed to the same degree as the capacity to produce ATP. This reversible metabolic suppression is reflected in explanted sartorius muscle (304) suggesting that the effect is intrinsic to the tissue and does not depend on central signals, making it a very useful experimental model.…”

Rapid mitochondrial adjustments in response to short-term hypoxia and re-oxygenation in the Pacific oysterCrassostrea gigas

“…Only after 3h of hypoxia, a decrease was apparent for state 3 and was significant for state 4. Decreasing respiratory rate is one of the first modifications during the onset of metabolic depression of hypoxiatolerant organisms and is crucial in the prevention of the onset of fatal oxygen depletion (Chandel et al, 1997;St-Pierre et al, 2000b;Bishop et al, 2002;Abele et al, 2007). Studies on hibernating amphibians suggest that a decrease in substrate oxidation and electron transport in the respiratory chain is the main mechanism reducing mitochondrial respiration (St-Pierre et al, 2000a).…”