Fiche publication
Date publication
août 2021
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr LATRUFFE Norbert
,
Dr ANDREOLETTI Pierre
,
Pr CHERKAOUI-MALKI Mustapha
Tous les auteurs :
Tahri-Joutey M, Andreoletti P, Surapureddi S, Nasser B, Cherkaoui-Malki M, Latruffe N
Lien Pubmed
Résumé
In mammalian cells, two cellular organelles, mitochondria and peroxisomes, share the ability to degrade fatty acid chains. Although each organelle harbors its own fatty acid β-oxidation pathway, a distinct mitochondrial system feeds the oxidative phosphorylation pathway for ATP synthesis. At the same time, the peroxisomal β-oxidation pathway participates in cellular thermogenesis. A scientific milestone in 1965 helped discover the hepatomegaly effect in rat liver by clofibrate, subsequently identified as a peroxisome proliferator in rodents and an activator of the peroxisomal fatty acid β-oxidation pathway. These peroxisome proliferators were later identified as activating ligands of Peroxisome Proliferator-Activated Receptor α (PPARα), cloned in 1990. The ligand-activated heterodimer PPARα/RXRα recognizes a DNA sequence, called PPRE (Peroxisome Proliferator Response Element), corresponding to two half-consensus hexanucleotide motifs, AGGTCA, separated by one nucleotide. Accordingly, the assembled complex containing PPRE/PPARα/RXRα/ligands/Coregulators controls the expression of the genes involved in liver peroxisomal fatty acid β-oxidation. This review mobilizes a considerable number of findings that discuss miscellaneous axes, covering the detailed expression pattern of PPARα in species and tissues, the lessons from several PPARα KO mouse models and the modulation of PPARα function by dietary micronutrients.
Mots clés
PPARα, PPARα knockout, PPRE, coregulator, ligand, micronutrients, peroxisome, β-oxidation
Référence
Int J Mol Sci. 2021 08 20;22(16):
