The respiration-impairing effect of rubroskyrin, a toxic metabolite.

The toxic effect of rubroskyrin, a modified bis-anthraquinone pigment fromPenicillium islandicum Sopp, on mitochondrial respiration has been studied by using isolated rat liver mitochondria, comparing with those of luteoskyrin and rugulosin which are well knownislandicum toxins. It was found that rubroskyrin exerted an uncoupling effect on mitochondrial respiration, abating the respiratory control ratio (RCR) by a dose dependent manner (UD50: 10 μM) and markedly depressed state 3 respiration at high concentrations, whereas such respiration-impairing effects of luteoskyrin and rugulosin were not detected at the concentrations tested (max. 35 μM). The involvement of redox-reaction was not detected in the uncoupling effect of the quinone pigment, rubroskyrin.Spectroscopic study at various pHs revealed that rubroskyrin possessed a pK value within the range of physiological pH, suggesting that rubroskyrin is a weak acid-type uncoupler capable of conducting protons across mitochondrial inner membrane.