Ca as cofactor of the mitochondrial H -translocating F F -ATP(hydrol)ase.

The mitochondrial F F -ATPase in the presence of the natural cofactor Mg acts as the enzyme of life by synthesizing ATP, but it can also hydrolyze ATP to pump H . Interestingly, Mg can be replaced by Ca , but only to sustain ATP hydrolysis and not ATP synthesis. When Ca inserts in F , the torque generation built by the chemomechanical coupling between F and the rotating central stalk was reported as unable to drive the transmembrane H flux within F . However, the failed H translocation is not consistent with the oligomycin-sensitivity of the Ca -dependent F F -ATP(hydrol)ase. New enzyme roles in mitochondrial energy transduction are suggested by recent advances. Accordingly, the structural F F -ATPase distortion driven by ATP hydrolysis sustained by Ca is consistent with the permeability transition pore signal propagation pathway. The Ca -activated F F -ATPase, by forming the pore, may contribute to dissipate the transmembrane H gradient created by the same enzyme complex.