The impairing effects of chaetochromin D on mitochondrial respiration and structure.

Chaetochromin D, a toxic secondary metabolite ofChaetomlum graclle, was examined for impairing effects on mitochondrial respiration and structure (swelling-induction) using isolated rat liver mitochondria to gain Insight into the molecular mechanism for Its cytotoxicity. Chaetochromin D exerted similar mode of effects to those of chaetochromin A, cephalochromin, and ustilaginoldin A on mitochondrial reactions, causing uncoupling of oxidative phosphorylation, depression of state 3 respiration, and induction of drastic swelling In mitochondria.Chaetochromin D induced the same style of swelling as that induced by chaetochromin A, being characterized by a very high rate and small amplitude of swelling. The swelling terminated In the middle and the amplitude was about half of the full swelling. Once the quick swelling ceased in the middle, subsequent swelling could not be elicited by the second addition of chaetochromin D at any of the concentrations tested.