Mitochondrial Permeability Transition in the CNS - Composition, Regulation, and Pathophysiological Relevance

Mitochondrial permeability transition (MPT) is induced in isolated brain mitochondria by calcium and oxidants and is inhibited by adenine nucleotides. When induced, MPT is associated with equilibration of solutes of <1500 Da across the inner mitochondrial membrane. A persistent induction of MPT depolarizes the inner membrane and causes cessation of ATP synthesis, swelling of the matrix, and bursting of the mitochondrial membranes. The rupture of the membranes releases calcium stored in the mitochondrial matrix and apoptogenic factors from the intermembrane space, leading to cell death. MPT has been implicated in acute brain injury and neurodegenerative disease since inhibitors of MPT such as cyclosporin A (CsA) are brain protective. Whether MPT has a physiological role is unclear, but MPT may be important in calcium homeostasis under conditions of excessive neuronal activity