1. Department of Molecular and Cellular Biology, University of California, Berkeley, California 94720-3112, USA

Correspondence to: George Oster¹ Correspondence and requests for materials should be addressed to G.O. (e-mail: Email: goster@nature.berkeley.edu).

Mitochondria, bacteria and chloroplasts use the free energy stored in transmembrane ion gradients to manufacture ATP by the action of ATP synthase. This enzyme consists of two principal domains. The asymmetric membrane-spanning F_o portion contains the proton channel, and the soluble F₁ portion contains three catalytic sites which cooperate in the synthetic reactions¹. The flow of protons through F_o is thought to generate a torque which is transmitted to F₁ by an asymmetric shaft, the coiled-coil -subunit. This acts as a rotating 'cam' within F₁, sequentially releasing ATPs from the three active sites^{1, 2, 3, 4, 5}. The free-energy difference across the inner membrane of mitochondria and bacteria is sufficient to produce three ATPs per twelve protons passing through the motor. It has been suggested that this protonmotive force biases the rotor's diffusion so that F_o constitutes a rotary motor turning the shaft⁶. Here we show that biased diffusion, augmented by electrostatic forces, does indeed generate sufficient torque to account for ATP production. Moreover, the motor's reversibility — supplying torque from ATP hydrolysis in F₁ converts the motor into an efficient proton pump⁷ — can also be explained by our model.