Mitochondrial metabolic suppression in fasting and daily torpor: consequences for reactive oxygen species production.

Abstract Daily torpor results in an ∼70% decrease in metabolic rate (MR) and a 20%-70% decrease in state 3 (phosphorylating) respiration rate of isolated liver mitochondria in both dwarf Siberian hamsters and mice even when measured at 37°C. This study investigated whether mitochondrial metabolic suppression also occurs in these species during euthermic fasting, when MR decreases significantly but torpor is not observed. State 3 respiration rate measured at 37°C was 20%-30% lower in euthermic fasted animals when glutamate but not succinate was used as a substrate. This suggests that electron transport chain complex I is inhibited during fasting. We also investigated whether mitochondrial metabolic suppression alters mitochondrial reactive oxygen species (ROS) production. In both torpor and euthermic fasting, ROS production (measured as H(2)O(2) release rate) was lower with glutamate in the presence (but not absence) of rotenone when measured at 37°C, likely reflecting inhibition at or upstream of the complex I ROS-producing site. ROS production with succinate (with rotenone) increased in torpor but not euthermic fasting, reflecting complex II inhibition during torpor only. Finally, mitochondrial ROS production was twofold more temperature sensitive than mitochondrial respiration (as reflected by Q(10) values). These data suggest that electron leak from the mitochondrial electron transport chain, which leads to ROS production, is avoided more efficiently at the lower body temperatures experienced during torpor.