Non-conventional mitochondrial permeability transition: Its regulation by mitochondrial dynamics

Mitochondrial permeability transition (MPT) is a phenomenon that the inner mitochondrial membrane (IMM) loses its selective permeability, leading to mitochondrial dysfunction and cell injury. Electrophysiological evidence indicates the presence of a mega-channel commonly called permeability transition pore (PTP) whose opening is responsible for MPT. However, the molecular identity of the PTP is still under intensive investigations and debates, although cyclophilin D that is inhibited by cyclosporine A (CsA) is the established regulatory component of the PTP. PTP can also open transiently and functions as a rapid mitochondrial Ca2+ releasing mechanism. Mitochondrial fission and fusion, the main components of mitochondrial dynamics, control the number and size of mitochondria, and have been shown to play a role in regulating MPT directly or indirectly. Studies by us and others have indicated the potential existence of a form of transient MPT that is insensitive to CsA. This non-conventional MPT is regulated by mitochondrial dynamics and may serve a protective role possibly by decreasing the susceptibility for a frequent or sustained PTP opening; hence, it may have a therapeutic value in many disease conditions involving MPT.

Automated summary

Mitochondrial permeability transition (MPT) is a phenomenon that leads to mitochondrial dysfunction and cell injury. The opening of a mega-channel called the permeability transition pore (PTP) is responsible for MPT. Mitochondrial fission and fusion play a role in regulating MPT. There may also exist a non-conventional form of MPT that is insensitive to certain inhibitors.