Bistability of Mitochondrial Respiration Underlies Paradoxical Reactive Oxygen Species Generation Induced by Anoxia
Figure 5
Theoretical predictions and experimental observations of the bistability in mitochondrial electron transport triggered by anoxia.
(A) shows that decrease of oxygen concentration down to 0.1% O2 and below induces a switch to high SQ content if initially the system is in a state characterized by low SQ content. The dependence of SQ content at Qo site of complex III was calculated using the oxygen dependence of complex IV activity summarized in eq (18) of Model section. The increase of SQ content at Qo site proceeds in conjunction with decrease of electron flow limited by oxygen availability. Dashed line shows the continuum of steady states for SQ content reached if initially mitochondria are in a high ROS producing state. In this case the increase of oxygen availability does not restore low levels of SQ radicals. (B) shows that mitochondria, switched to a low ROS producing state by a temporal presence of ADP (as in (Fig 4A), could be switched back to high ROS production by a short application of anoxia (red trace), which is in accordance with the model prediction shown in Figure 4A. Anoxia was induced by substitution of atmospheric O2 for N2 and its effectiveness was estimated by the decrease of transmembrane potential (blue trace). After reoxygenation followed by restoration of membrane potential, ROS production is essentially higher than before anoxia.