Figure 1. Calcium and reactive oxygen species (ROS) lead to activation of the mitochondrial PTP (permeability transition pore) and initiation of cell death.

A, At the end of ischemia and the first few seconds of reperfusion, an increase in mitochondrial calcium can occur via MCU (mitochondrial calcium uniporter) which can activate PTP. There is also a buildup of succinate which upon conversion to fumarate by complex II, generates large levels of QH2 (ubiquinol) which drives reverse electron transport (RET) of complex I leading to ROS production. As shown in B, inhibition of PTP,. inhibition of MCU and inhibition of complex II (or complex I) are potential mechanisms to reduce PTP opening and reduce cell death. CypD indicates cyclophilin D. Illustration credit: Ben Smith.