File:Gnaiger 2001 Respir Physiol New Fig10.jpg

Opposite effects of ADP limitation and oxygen limitation on mitochondrial membrane potential, and LEAK oxygen flux. The LEAK state is obtained when total oxygen flux equals LEAK respiration. In all other respiratory states, total oxygen flux is the sum of LEAK oxygen flux and mechanistically coupled oxygen flux. A: ADP limitation of respiration at high oxygen levels in the transition from the OXPHOS state (saturating ADP) or active State 3 to the resting LEAK state leads to an increase of membrane potential and exponential acceleration of the proton leak (heavy line). Because LEAK oxygen flux increases while total oxygen flux is reduced, the ATP yield declines to zero. Turnover-dependent proton leaks increase the LEAK oxygen flux in the OXPHOS state but decline towards the LEAK state. Mitochondrial production of reactive oxygen species (ROS) increases with membrane potential towards the LEAK state, and ROS-linked electron bypass contributes minimally to LEAK oxygen flux at high oxygen. On the right, the decline of ADP/O₂ flux ratios is shown in the transition from OXPHOS to LEAK. B: Oxygen limitation of respiration causes a reduction of membrane potential in the transition from ADP limitation at high oxygen, to intracellular conditions of low oxygen and low ADP, to finally severe oxygen limitation under hypoxia and anoxia. Potentially synergistic with the well documented membrane potential effect on LEAK flux, are the hypothetical effects of decreasing membrane permeability and suppression of ROS production under hypoxia (modified from Gnaiger 2011).