Permeability transition pore of the inner mitochondrial membrane can operate in two open states with different selectivities.
Prooxidants induce release of Ca2+ from mitochondria through the giant solute pore in the mitochondrial inner membrane. However, under appropriate conditions prooxidants can induce Ca2+ release without inducing a nonspecific permeability change. Prooxidant-induced release of Ca2+ is selective. Presumably, this is the result of the operation of a permeability pathway for H+ coupled to the reversal of the Ca2+ uniporter, the latter generating the selectivity. The solute pore and prooxidant-induced Ca2+-specific pathways exhibit common sensitivities to a set of inhibitors and activators. It is proposed that the pore can operate in two open states: (1) permeable to H+ only and (2) permeable to solutes of M(r) < 1500. Under some conditions, prooxidants induce the H+-selective state which, in turn, collapses the inner membrane potential and permits selective loss of Ca2+ via the Ca2+ uniporter.
Novgorodov
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SA
A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Gudz
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TI
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D017136:Ion Transport; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D016877:Oxidants / Q000494:pharmacology; D010539:Permeability; D011522:Protons; D012964:Sodium / Q000378:metabolism
D015220:Calcium Channels; D016877:Oxidants; D011522:Protons; D012964:Sodium