What happens when the mitochondrial H+-translocating F1FO-ATP(hydrol)ase becomes a molecular target of calcium? The pore opens.

The F1FO-ATPase has Mg2+ 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 Ca2+ with the enzyme and the modification of the biological role. Three distinct binding regions of Ca2+ have been localized on the enzyme complex: one in the F1 catalytic sites and the other two sites in the membrane-embedded domain FO. In all likelihood, Ca2+-activated enzyme most frequently works as an H+-translocating F1FO-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 F1FO-ATPase could reveal the molecular mechanism of pore opening when Ca2+ is bound to the enzyme. In this regard, the role of Ca2+-dependent function of the F1FO-ATPase in the formation of the mPTP is discussed.