Mitochondrial intermembrane junctional complexes and their role in cell death

A mitochondrial complex comprising the voltage-dependent anion channel (out er membrane), the adenine nucleotide translocase (inner membrane) and cyclo philin-D (matrix) assembles at contact sites between the inner and outer me mbranes. Under pathological conditions associated with ischaemia and reperf usion the junctional complex 'deforms' into the permeability transition (PT ) pore, which can open transiently, allowing free permeation of low M-r sol utes across the inner membrane. This may be a critical step in the pathogen esis of lethal cell injury in ischaemia and reperfusion. Moreover, it is ar gued, the degree of pore opening may be an important determinant of the rel ative extent of apoptosis and necrosis under these conditions. In addition, mitochondria are the major sites of action of Pax and other apoptotic regu latory proteins of the Bcl-2 family. These proteins control a mitochondrial amplificatory loop in the apoptotic signalling pathway in which cytochrome c and other apoptogenic proteins of the mitochondrial intermembrane space are released into the cytosol. There are indications that the junctional co mplex, or components of it, may also mediate the action of Bax, but in a wa y that does not involve PT pore formation.