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The respiration-impairing effect of rubroskyrin, a toxic metabolite

S Mori1, Y Sugihara, A Kitagawa

  • 1Department of Biochemistry, Gifu University School of Medicine, 500, Gifu, Japan.

Mycotoxin Research
|April 23, 2013
PubMed

Insights

Rubroskyrin, a fungal pigment, disrupts mitochondrial respiration by uncoupling oxidative phosphorylation. Unlike related toxins, it significantly impairs energy production in isolated rat liver mitochondria.

Area of Science:

  • Biochemistry
  • Toxicology
  • Mitochondrial Physiology

Background:

  • Penicillium islandicum Sopp produces toxic bis-anthraquinone pigments.
  • Luteoskyrin and rugulosin are known toxins from this fungus.
  • The toxic mechanisms of these pigments, particularly rubroskyrin, require further elucidation.

Purpose of the Study:

  • To investigate the toxic effects of rubroskyrin on mitochondrial respiration.
  • To compare the effects of rubroskyrin with luteoskyrin and rugulosin.
  • To determine the mechanism of rubroskyrin-induced mitochondrial dysfunction.

Main Methods:

  • Isolated rat liver mitochondria were used as the experimental model.
  • Mitochondrial respiration was assessed using techniques to measure oxygen consumption.
  • Spectroscopic analysis was employed to determine rubroskyrin's acid-base properties.

Main Results:

  • Rubroskyrin demonstrated a dose-dependent uncoupling effect on mitochondrial respiration, reducing the respiratory control ratio (RCR) with a UD50 of 10 μM.
  • High concentrations of rubroskyrin markedly depressed state 3 respiration.
  • Luteoskyrin and rugulosin did not exhibit significant respiration-impairing effects at tested concentrations (up to 35 μM).
  • No involvement of redox reactions was detected in rubroskyrin's uncoupling effect.
  • Spectroscopic studies indicated rubroskyrin has a pK within the physiological pH range.

Conclusions:

  • Rubroskyrin acts as a weak acid-type uncoupler, facilitating proton transport across the inner mitochondrial membrane.
  • Rubroskyrin exhibits greater toxicity towards mitochondrial respiration compared to luteoskyrin and rugulosin.
  • The uncoupling mechanism of rubroskyrin is independent of redox cycling.

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