From the Ca 2+ -activated F 1 F O -ATPase to the mitochondrial permeability transition pore: an overview.

Based on recent advances on the Ca2+ -activated F1 FO -ATPase features, a novel multistep mechanism involving the mitochondrial F1 FO complex in the formation and opening of the still enigmatic mitochondrial permeability transition pore (MPTP), is proposed. MPTP opening makes the inner mitochondrial membrane (IMM) permeable to ions and solutes and, through cascade events, addresses cell fate to death. Since MPTP forms when matrix Ca2+ concentration rises and ATP is hydrolyzed by the F1 FO -ATPase, conformational changes, triggered by Ca2+ insertion in F1 , may be transmitted to FO and locally modify the IMM curvature. These events would cause F1 FO -ATPase dimer dissociation and MPTP opening.