The mitochondrial F1FO-ATPase in the presence of the natural cofactor
Mg2+ acts as the enzyme of life by synthesizing ATP, but it can also
hydrolyze ATP to pump H+. Interestingly, Mg2+ can be replaced by Ca2+,
but only to sustain ATP hydrolysis and not ATP synthesis. When Ca2+
inserts in F1, the torque generation built by the chemomechanical
coupling between F1 and the rotating central stalk was reported as
unable to drive the transmembrane H+ flux within FO. However, the failed
H+ translocation is not consistent with the oligomycin-sensitivity of
the Ca2+-dependent F1FO-ATP(hydrol)ase. New enzyme roles in
mitochondrial energy transduction are suggested by recent advances.
Accordingly, the structural F1FO-ATPase distortion driven by ATP
hydrolysis sustained by Ca2+ is consistent with the permeability
transition pore signal propagation pathway. The Ca2+-activated
F1FO-ATPase, by forming the pore, may contribute to dissipate the
transmembrane H+ gradient created by the same enzyme complex.