Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

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 beta-oxidation pathway, a distinct mitochondrial system feeds the oxidative phosphorylation pathway for ATP synthesis. At the same time, the peroxisomal beta-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 beta-oxidation pathway. These peroxisome proliferators were later identified as activating ligands of Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha), cloned in 1990. The ligand-activated heterodimer PPAR alpha/RXR alpha 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/PPAR alpha/RXR alpha/ligands/Coregulators controls the expression of the genes involved in liver peroxisomal fatty acid beta-oxidation. This review mobilizes a considerable number of findings that discuss miscellaneous axes, covering the detailed expression pattern of PPAR alpha in species and tissues, the lessons from several PPAR alpha KO mouse models and the modulation of PPAR alpha function by dietary micronutrients.

Automated summary

This article discusses the shared ability of mitochondria and peroxisomes in degrading fatty acid chains, the hepatomegaly effect caused by clofibrate, the identification of peroxisome proliferators and their impact on the peroxisomal fatty acid beta-oxidation pathway, and the modulation of PPAR alpha function by dietary micronutrients.