The effect of peroxisome proliferators on mitochondrial bioenergetics

Shaoyu Zhou, Kendall B Wallace

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Peroxisome proliferators are a group of structurally diverse chemicals that cause the proliferation of peroxisomes in rodents. The purpose of this investigation was to test the hypothesis that the shared effect of these compounds on peroxisome proliferation is mediated through a common inhibitory effect on mitochondrial bioenergetics. Freshly isolated rat liver mitochondria were energized with succinate. The effect of the chemicals on mitochondrial bioenergetics was analyzed by monitoring calcium-induced changes in membrane potential and swelling, as well as changes in mitochondrial respiration. Mitochondrial membrane potential was measured with a TPP+-sensitive electrode, and swelling was recorded spectrophotometrically. Mitochondrial oxygen uptake was monitored with a Clark-type oxygen electrode. Gemfibrozil and WY-14,643 induced the mitochondrial permeability transition as characterized by calcium-induced swelling and depolarization of membrane potential, both of which were inhibited by cyclosporine A. Fenofibrate, clofibrate, ciprofibrate and diethylhexyl phthalate, on the other hand, caused a direct dose-dependent depolarization of mitochondrial membrane potential. However, the mechanism of membrane depolarization varied among the test chemicals. Bezafibrate and trichloroethylene elicited no effect on succinate-supported mitochondrial bioenergetics. The results of this investigation demonstrate that although most, but not all, peroxisome proliferators interfere with mitochondrial bioenergetics, the specific biomolecular mechanism differs among the individual compounds.

Original languageEnglish (US)
Pages (from-to)82-89
Number of pages8
JournalToxicological Sciences
Issue number1
StatePublished - 1999


  • Membrane potential
  • Mitochondria
  • Permeability
  • Peroxisome proliferator
  • Respiration


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