THE MECHANISM FOR THE ATP-INDUCED UNCOUPLING OF RESPIRATION IN MITOCHONDRIA OF THE YEAST SACCHAROMYCES-CEREVISIAE

We have recently reported that ATP induces an uncoupling pathway in Sa ccharomyces cerevisiae mitochondria [Prieto, Bouillaud, Ricquier and R ial (1992) Eur. J. Biochem. 208, 487-491]. The presence of this pathwa y would explain the reported low efficiency of oxidative phosphorylati on in S. cerevisiae, and may represent one of the postulated energy-di ssipating mechanisms present in these yeasts. In this paper we demonst rate that ATP exerts its action in two steps: first, at low ATP/P-i ra tios, it increases the respiratory-chain activity, probably by alterin g the kinetic properties of cytochrome c oxidase. Second, at higher AT P/P-i ratios, an increase in membrane permeability leads to a collapse in membrane potential. The ATP effect on cytochrome c oxidase corrobo rates a recent report showing that ATP interacts specifically with yea st cytochrome oxidase, stimulating its activity [Taanman and Capaldi ( 1993) J. Biol. Chem. 268, 18754-18761].