Structural organization of mitochondrial ATP synthase.

Specific modules and subcomplexes like F(1) and F(0)-parts, F(1)-c subcomplexes, peripheral and central stalks, and the rotor part comprising a ring of c-subunits with attached subunits gamma, delta, and epsilon can be identified in yeast and mammalian ATP synthase. Four subunits, alpha(3)beta(3), OSCP, and h, seem to form a structural entity at the extramembranous rotor/stator interface (gamma/alpha(3)beta(3)) to hold and stabilize the rotor in the holo-enzyme. The intramembranous rotor/stator interface (c-ring/a-subunit) must be dynamic to guarantee unhindered rotation. Unexpectedly, a c(10)a-assembly could be isolated with almost quantitive yield suggesting that an intermediate step in the rotating mechanism was frozen under the conditions used. Isolation of dimeric a-subunit and (c(10))(2)a(2)-complex from dimeric ATP synthase suggested that the a-subunit stabilizes the same monomer-monomer interface that had been shown to involve also subunits e, g, b, i, and h. The natural inhibitor protein Inh1 does not favor oligomerization of yeast ATP synthase. Other candidates for the oligomerization of dimeric ATP synthase building blocks are discussed, e.g. the transporters for inorganic phosphate and ADP/ATP that had been identified as constituents of ATP synthasomes. Independent approaches are presented that support previous reports on the existence of ATP synthasomes in the mitochondrial membrane.