Transcriptional Regulation of the Mitochondrial Citrate and Carnitine/Acylcarnitine Transporters: Two Genes Involved in Fatty Acid Biosynthesis and β-oxidation.
Transcriptional Regulation of the Mitochondrial Citrate and Carnitine/Acylcarnitine Transporters: Two Genes Involved in Fatty Acid Biosynthesis and β-oxidation.
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DOI：
10.3390/biology2010284
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发表时间：
2013-01-29
期刊：
影响因子：
4.2
通讯作者：
Palmieri F
中科院分区：
文献类型：
--
作者：
Iacobazzi V;Infantino V;Palmieri F
参与脂肪酸代谢的基因的转录调控被认为是控制脂质稳态的主要长期调控机制。通过这一机制，转录因子、营养物质、激素和表观遗传学不仅控制脂肪酸代谢，还在分子水平上控制许多代谢途径和细胞功能。许多基因在转录水平上的表达调控已经被分析过。本文综述了线粒体载体基因家族SLC25中参与脂肪酸生物合成和氧化的两个基因：柠檬酸载体（CIC）和肉碱/酰基肉碱/载体（CAC）的转录调控。讨论了组织特异性和非组织特异性转录因子在激活或抑制CIC和CAC基因表达中的作用。一些转录因子（如PPAR和FOXA1）与药物的相互作用，以及这种相互作用如何成为一种有吸引力的治疗方法，也得到了评估。此外，CIC和CAC基因的表达通过激素和营养变化以及表观遗传学的协调反应来调节的机制也得到了强调。
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.