From the Ca-activated FF-ATPase to the mitochondrial permeability transition pore: an overview.

Based on recent advances on the Ca-activated FF-ATPase features, a novel multistep mechanism involving the mitochondrial FF 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 Ca concentration rises and ATP is hydrolyzed by the FF-ATPase, conformational changes, triggered by Ca insertion in F, may be transmitted to F and locally modify the IMM curvature. These events would cause FF-ATPase dimer dissociation and MPTP opening.