The effects of cytochalasin-B on the membranes of enzymatically active mitochondria

Cytochalasin-B, one of a series of structurally related metabolites obtained from the moldHelminthosporium dematioideum, has been shown to alter several partial reaction parameters associated with mitochondrial oxidative phosphorylation. State-3 (active) respiratory rates, respiratory control ratios and overall ATPase activity were all inhibited by cytochalasin-B at concentrations between 0.2 and 1.0 mM. However, the efficiency of coupled oxidative phosphorylation, evaluated by the ADP/O ratio, was not significantly affected. Therefore, the metabolite does not appear to act at enzymic loci directly affiliated with the coupling mechanism of oxidative phosphorylation. The mode of action of cytochalasin-B may be conceived as restricting diffusion by means of macromolecular conformational changes occurring within the mitochondrial membranes. Electron micrographs of paired, 10 min mitochondrial incubations, in the presence and absence of 1.0 mM cytochalasin-B, clearly display a structural alteration within these organelles, such that upon the binding of cytochalasin-B the matrix area decreases and the inner membrane cristae develop condensed, tubular distortions.