New molecular aspects of regulation of mitochondrial activity by fenofibrate and fasting

FEBS Lett. 2000 Sep 29;482(1-2):71-4. doi: 10.1016/s0014-5793(00)02023-8.

Abstract

Fenofibrate and fasting are known to regulate several genes involved in lipid metabolism in a similar way. In this study measuring several mitochondrial enzyme activities, we demonstrate that, in contrast to citrate synthase and complex II, cytochrome c oxidase (COX) is a specific target of these two treatments. In mouse liver organelles, Western blot experiments indicated that mitochondrial levels of p43, a mitochondrial T3 receptor, and mitochondrial peroxisome proliferator activated receptor (mt-PPAR), previously described as a dimeric partner of p43 in the organelle, are increased by both fenofibrate and fasting. In addition, in PPAR alpha-deficient mice, this influence was abolished for mt-PPAR but not for p43, whereas the increase in COX activity was not altered. These data indicate that: (1) PPAR alpha is involved in specific regulation of mt-PPAR expression by both treatments; (2) fenofibrate and fasting regulate the mitochondrial levels of p43 and thus affect the efficiency of the direct T3 mitochondrial pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citrate (si)-Synthase / metabolism
  • Crosses, Genetic
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Electron Transport Complex II
  • Electron Transport Complex IV / metabolism
  • Fasting
  • Fenofibrate / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / enzymology
  • Mitochondria, Liver / physiology*
  • Multienzyme Complexes / metabolism
  • Organelles / drug effects
  • Organelles / physiology
  • Oxidoreductases / metabolism
  • Receptors, Cytoplasmic and Nuclear / deficiency
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Succinate Dehydrogenase / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • Multienzyme Complexes
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Oxidoreductases
  • Electron Transport Complex II
  • Succinate Dehydrogenase
  • Electron Transport Complex IV
  • Citrate (si)-Synthase
  • Fenofibrate