New molecular aspects of regulation of mitochondrial activity by fenofibrate and fasting.
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.
Casas
F
F
UMR Différenciation Cellulaire et Croissance (INRA-UMII-ENSAM), Unité d'Endocrinologie Cellulaire, Institut National de la Recherche Agronomique (INRA) 34060 Montpellier Cedex 1, France.
Pineau
T
T
Rochard
P
P
Rodier
A
A
Daury
L
L
Dauça
M
M
Cabello
G
G
Wrutniak-Cabello
C
C
D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV / Q000378:metabolism; D005215:Fasting; D011345:Fenofibrate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009097:Multienzyme Complexes / Q000378:metabolism; D015388:Organelles / Q000187:drug effects / Q000502:physiology; D010088:Oxidoreductases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D011345:Fenofibrate