Inhibition of the soluble mitochondrial soluble ATPase (F1) by polygodial

MARÍA V. CASTELLI; ANABELLA F. LODEYRO; SUSANA A. S. ZACCHINO; OSCAR A. ROVERI

Buenos Aires, ARGENTINA.

Congreso; XIV Congreso Internacional de Biofísica; 2002

International Union for Pure and Applied Biophysics, Sociedad Argentina de Biofísica

INHIBITION OF THE MITOCHONDRIAL SOLUBLE ATPase (F1) BY POLYGODIAL. Polygodial is a potent antifungal agent isolated from plants belonging to Polygonaceae, Canellaceae and Winteraceae families. It has been postulated that it exerts its action by inhibition of the mitochondrial ATPase (Lunde, C.S. and Kubo, I. (2000) Antimicrob. Agents Chemother. 44, 1943 –1953). We have recently reported that polygodial inhibited ATP synthesis in beef-heart submitochondrial particles at concentrations (I50=2mM) that did not affect electron transport. Higher [polygodial] also inhibited ATPase activity in SMP (I50=100mM). On the other hand, polygodial stimulated the basal ATPase activity and the electron transport in state “4” in rat liver mitochondria. The ATPase activity of the mitochondrial F1 is inhibited by polygodial in a time dependent manner. The final inhibition is complete at 0.25 mM ATP, whereas at 1 mM ATP it is about 80%. The velocity of ATP hydrolysis followed single exponential decays with half times of 140 and 50 seconds respectively. Also a single exponential decay (t½=500 seconds) was observed when F1 was preincubated with 0.8 mM polygodial. In summary, polygodial is an irreversible inhibitor of F1 that follows a complex kinetic behavior. However, this effect is produced at [polygodial] much larger than those that inhibited ATP synthesis.