Tissue Specific Sensitivity of Mitochondrial Permeability Transition Pore to Ca2+ Ions.

Recent data in the literature have shown that mitochondria play an important role in induction of apoptotic and necrotic processes (9) and that mitochondrial membrane permeability transition pore (MPTP) is involved in cell death processes (3, 10). Opening of this pore is induced by impaired intracellular homeostasis of calcium ions; sensitivity to calcium is modified by many factors from which oxygen radicals are the most important (2, 8, 13, 14, 16). When the pore is opened mitochondrial membrane potential is discharged and aerobic ATP generation is depressed. Mitochondrial swelling due to equilibration of ion and water gradient between cytosol and mitochondrial matrix is accompanied by rupture of outer mitochondrial membrane and release of cytochrome c which activates caspases and apoptotic reactions (12, 17, 18, 19, 20). Two criteria are used as evidence that MPTP is responsible for mitochondrial swelling and various accompanying reactions: calcium activation of particular reactions and their inhibition by EGTA, cyclosporine A (4, 11), or sanglifehrin A (7). In spite of its importance in pathogenesis of many diseases in which apoptotic and necrotic processes are involved, knowledge about the structural organization, functional activity and regulation of MPTP is not sufficient (3, 14). In our work we focused on problems concerning tissue specific regulation of MPTP function because it has been shown that there exists physiological diversity of mitochondrial processes in various tissues (1). Recently, Panov et al. (16) observed specific differences in tolerance to calcium-induced swelling between liver and brain mitochondria. We present complementary additional data showing that also heart mitochondria are more resistant to calciuminduced opening of membrane permeability transition pore when compared with liver mitochondria.