Mitochondrial ATP synthase: Fifteen years later

Mitochondrial F-o. F-1-H+-ATP synthase is the main enzyme responsible for t he formation of ATP in aerobic cells. An alternating binding change mechani sm is now generally accepted for the operation of the enzyme. This mechanis m apparently leaves no room for the participation of nucleotides and P-i ot her than sequential binding to (release from) the catalytic sites. However, the kinetics of ATP hydrolysis by mitochondrial ATPase is very complex, an d it is difficult to explain it in terms of the alternating binding change mechanism only. F-o. F-1 catalyzes both <Delta(mu)over bar>(H+)-dependent A TP synthesis and ATP-dependent <Delta(mu)over bar>(H+) generation. It is ge nerally believed that this enzyme operates as the smallest molecular electr omechanochemical reversible machine. This essay summarizes data which contr adict this simple reversible mechanism and discusses a hypothesis in which different pathways are followed for ATP hydrolysis and ATP synthesis, A mod el for a reversible switch mechanism between ATP hydrolase and ATP synthase states of F-o. F-1 is proposed.