What happens when the mitochondrial H-translocating FF-ATP(hydrol)ase becomes a molecular target of calcium? The pore opens.

The FF-ATPase has Mg cofactor as the natural divalent cation to support the bifunctional activity of ATP synthesis and hydrolysis. Different physio(patho)logical conditions permit the molecular interaction of Ca with the enzyme and the modification of the biological role. Three distinct binding regions of Ca have been localized on the enzyme complex: one in the F catalytic sites and the other two sites in the membrane-embedded domain F. In all likelihood, Ca-activated enzyme most frequently works as an H-translocating FF-ATP(hydrol)ase with a monofunctional activity that triggers the formation of mitochondrial permeability transition pore (mPTP) phenomenon. The protein(s) component of the mPTP is considered an arcane mystery. However, the FF-ATPase could reveal the molecular mechanism of pore opening when Ca is bound to the enzyme. In this regard, the role of Ca-dependent function of the FF-ATPase in the formation of the mPTP is discussed.