The mitochondrial citrate carrier: Metabolic role and regulation of its activity and expression

Abstract

SummaryThe citrate carrier (CiC), a nuclear-encoded protein located in the mitochondrial inner membrane, is a member of the mitochondrial carrier family. CiC plays an important role in hepatic lipogenesis, which is responsible for the efflux of acetyl-CoA from the mitochondria to the cytosol in the form of citrate, the primer for fatty acid and cholesterol synthesis. In addition, CiC is a key component of the isocitrate-oxoglutarate and the citrate-malate shuttles. CiC has been purified from various species and its reconstituted function characterized as well as its cDNA isolated and sequenced. CiC mRNA and/or CiC protein levels are high in liver, pancreas, and kidney, but are low or absent in brain, heart, skeletal muscle, placenta, and lungs. A reduction of CiC activity was found in diabetic, hypothyroid, starved rats, and in rats fed on a polyunsaturated fatty acid (PUFA)-enriched diet. Molecular analysis suggested that the regulation of CiC activity occurs mainly through transcriptional and post-transcriptional mechanisms. This review begins with an assessment of the current understanding of CiC structural and biochemical characteristics, underlying the structure-function relationship. Emphasis will be placed on the molecular basis of the regulation of CiC activity in coordination with fatty acid synthesis.

Participation of citric acid and isocitric acid in the diurnal cycle of carboxylation and decarboxylation in the common ice plant

“…Additionally, transport of carboxylic acids through the inner mitochondrial membrane may also be mediated by a citrate carries, CICs (Picault et al 2004). CICs, also known as tricarboxylate carriers, exchange a dibasic form of tricarboxylic acids (citrate, isocitrate, and cis-aconitate) for another tricarboxylic acids, dicarboxylic acids (i.e., malate or succinate) or PEP (Gnoni et al 2009). As concluded by Wiskich and Dry (1985), export of citrate is more probable than of isocitrate, due to the aconitase equilibrium.…”

Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms

“…Through mitochondrial pyruvate carrier (MPC), the pyruvate enters the mitochondrion [39], where, by the action of pyruvate dehydrogenase, it is converted into acetyl-CoA, which condenses with oxaloacetate to form citrate in the TCA cycle. When cellular energy is in excess, TCA cycle is inhibited, and the produced citrate exits the mitochondrion through the citrate carrier (CiC), localized in the IMM [40,41,42]. Once in the cytosol, by the action of ATP citrate lyase (ACLY), citrate is reconverted in oxalacetate (OAA) and acetyl-CoA, which represents the primer for DNL.…”

Developmental expression of sideroflexin family genes in Xenopus embryos

“…Mitochondrial carriers (MCs), encoded in human by SLC25 genes, are membrane-embedded proteins that are normally localized in the inner membrane of mitochondria, where they confer a highly selective permeability and facilitate the flux of a large number of metabolites between mitochondria and cytosol (Hediger et al, 2004;Palmieri, 2004;Gnoni et al, 2009). Thus, MCs occupy a prominent position within eukaryotic cell intermediary metabolism.…”