REVIEW: Mitochondrial ATP Synthase: Fifteen Years Later

A. D. Vinogradov

Department of Biochemistry, School of Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (7-095) 939-3955; E-mail: adv@biochem.bio.msu.su

Received June 21, 1999

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Mitochondrial F_o·F₁-H⁺-ATP synthase is the main enzyme responsible for the formation of ATP in aerobic cells. An alternating binding change mechanism is now generally accepted for the operation of the enzyme. This mechanism apparently leaves no room for the participation of nucleotides and P_i other than sequential binding to (release from) the catalytic sites. However, the kinetics of ATP hydrolysis by mitochondrial ATPase is very complex, and it is difficult to explain it in terms of the alternating binding change mechanism only. F_o·F₁ catalyzes both Deltaµ_H+-dependent ATP synthesis and ATP-dependent Deltaµ_H+ generation. It is generally believed that this enzyme operates as the smallest molecular electromechanochemical reversible machine. This essay summarizes data which contradict this simple reversible mechanism and discusses a hypothesis in which different pathways are followed for ATP hydrolysis and ATP synthesis. A model for a reversible switch mechanism between ATP hydrolase and ATP synthase states of F_o·F₁ is proposed.

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KEY WORDS: F_o·F₁-ATPase, ATP synthase, reversibility of enzyme catalysis, mitochondria

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