Transcriptional Regulation of the Mitochondrial Citrate and Carnitine/Acylcarnitine Transporters: Two Genes Involved in Fatty Acid Biosynthesis and β-oxidation

Abstract

Transcriptional regulation of genes involved in fatty acid metabolism is considered the major long-term regulatory mechanism controlling lipid homeostasis. By means of this mechanism, transcription factors, nutrients, hormones and epigenetics control not only fatty acid metabolism, but also many metabolic pathways and cellular functions at the molecular level. The regulation of the expression of many genes at the level of their transcription has already been analyzed. This review focuses on the transcriptional control of two genes involved in fatty acid biosynthesis and oxidation: the citrate carrier (CIC) and the carnitine/ acylcarnitine/carrier (CAC), which are members of the mitochondrial carrier gene family, SLC25. The contribution of tissue-specific and less tissue-specific transcription factors in activating or repressing CIC and CAC gene expression is discussed. The interaction with drugs of some transcription factors, such as PPAR and FOXA1, and how this interaction can be an attractive therapeutic approach, has also been evaluated. Moreover, the mechanism by which the expression of the CIC and CAC genes is modulated by coordinated responses to hormonal and nutritional changes and to epigenetics is highlighted.

Keywords

• citrate carrier
• carnitine carrier
• gene expression
• mitochondrial transporters
• transcriptional regulation