Figure 2.

Schematic diagram of the PTP opening hypothesis. As illustrated in the figure above, an increasing level of Ca²⁺ and/or ROS in the mitochondrial matrix promotes the opening of high conductance of the PTP. This process is achieved by combining CyPD with PTP. Therefore, drugs targeting CypD, such as CsA, or genetic interventions for CyPD reduction can be applied without affecting PTP opening. Recently, Ca²⁺-induced PTP opening via small conductance PTP has been reported, and this process inhibits CsA. However, the same protein with different conformations may form pores of increasing size. CsA, cyclosporin A; CyPD, cyclophylin D; IMM, inner mitochondrial membrane; ROS, reactive oxygen species.