The MPTP was originally discovered by Haworth and Hunter  in 1979 and has been found to be involved in neurodegeneration, hepatotoxicity from Reye-related agents, cardiac necrosis and nervous and muscular dystrophies among other deleterious events inducing cell damage and death.
MPT is one of the major causes of cell death in a variety of conditions.  For example, it is key in neuronal cell death in excitotoxicity, in which overactivation of glutamate receptors causes excessive calcium entry into the cell.  MPT also appears to play a key role in damage caused by ischemia, as occurs in a heart attack and stroke. However, research has shown that the MPT pore remains closed during ischemia, but opens once the tissues are reperfused with blood after the ischemic period, playing a role in reperfusion injury.
MPT is also thought to underlie the cell death induced by Reye's syndrome, since chemicals that can cause the syndrome, like salicylate and valproate, cause MPT.  MPT may also play a role in mitochondrial autophagy. Cells exposed to toxic amounts of Ca ionophores also undergo MPT and death by necrosis.