New molecular aspects of regulation of mitochondrial activity by fenofibrate and fasting |
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Authors: | Casas F Pineau T Rochard P Rodier A Daury L Dauça M Cabello G Wrutniak-Cabello C |
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Institution: | UMR Différenciation Cellulaire et Croissance (INRA-UMII-ENSAM), Unité d'Endocrinologie Cellulaire, Institut National de la Recherche Agronomique (INRA) 34060 Montpellier Cedex 1, France. |
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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. |
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