The mitochondrial permeability transition pore components

The mitochondrial permeability transition pore (MPTP) is a non-specific channel in \nthe inner mitochondrial membrane (IMM) that opens following ischaemia and \nreperfusion due to the presence of various stimuli, such as oxidative stress, elevated \nphosphate concentration, and adenine nucleotide depletion. MPTP opening causes \nthe mitochondria to swell and become dysfunctional. This results in cell death, \nespecially by necrosis, due to the loss of oxidative phosphorylation and the \nsubsequent drop in adenosine triphosphate levels. In search of the identity of the \npore numerous studies have been done by several research groups in the last three \ndecades. For many years a widely accepted hypothesis prevailed suggesting the \ninvolvement of the adenine nucleotide translocase (ANT) and voltage-dependent \nanion channel (VDAC) as core proteins of the MPTP. Recent genetic studies, \nhowever, contradict this hypothesis and ascribe only a regulatory role to the ANT. \nFurthermore, there is now sufficient evidence to conclude that VDAC plays no role in \nmitochondrial permeability transition. In a recent study it was suggested that the \nmitochondrial phosphate carrier (PiC) may fulfil a role as a pore component. \nAccording to a proposed model MPTP is formed as a consequence of a \nconformational change in the PiC, triggered by calcium binding. Opening of the pore \nmay be enhanced through interactions with the ANT in the “c” conformation and \ncyclophilin-D, a mitochondrial matrix protein.