Figure 1

Mitochondrial rheostat of cell survival control. Key players in the regulation of mitochondrial function are depicted under four different states. Intracellular signaling is represented by bold arrows, filled light grey for survival or dark grey for pro-apoptotic signaling. Under normal conditions cells tolerate a certain level of stress before strong pro-apoptotic stimuli eventually perturb cellular homeostasis. A tumor cell no longer is in a state of equilibrium as ROS levels usually are high, survival signals are enhanced and extra-mitochondrial energy production may become predominant. During ischemia/hypoxia oxidative phosphorylation is disturbed leading to a decrease in ATP. Additionally, cells suffer from elevated ROS and Ca²⁺ levels. During reperfusion/reoxygenation mitochondrial ROS and Ca²⁺ levels peak and cell death may follow. Various intracellular signaling pathways are activated during this time and may positively or negatively control mitochondrial function. Eventually, a therapy that abolishes pro-apoptotic signals or elicits survival signaling may help to prevent or limit damage occurring under these conditions.