Crosstalk between Calcium and ROS in Pathophysiological Conditions

Figure 3

Regulation of mitochondrial Ca²⁺ uptake controls energy metabolism, mtROS production, and cell death. mtROS represent a by-product of oxidative phosphorylation and exert a beneficial or detrimental effect depending on their concentration and on the biological contest. In physiological conditions, mitochondrial Ca²⁺ uptake stimulates the TCA cycle and ATP production (left part). At physiological [Ca²⁺]_mit, the amount of ROS is counteracted by the activity of the antioxidant system (left part). In pathological conditions, excessive Ca²⁺ accumulation by mitochondria (right part) increases mtROS production which, in turn, affects antioxidant response. Altogether, this leads to the increase in the mPTP open probability, leading to irreversible collapse of the mitochondrial membrane potential, swelling of mitochondria, and thus release of cytochrome c, culminating in cell death.