The mitochondrial citrate carrier: metabolic role and regulation of its activity and expression.
The 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.
Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Science and Technologies, University of Salento, 73100 Lecce, Italy. gabriele.gnoni@unisalento.it
Gabriele V
GV
Gnoni
Paola
P
Priore
Math J H
MJ
Geelen
Luisa
L
Siculella
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019343:Citric Acid / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005544:Forecasting; D005786:Gene Expression Regulation; D007700:Kinetics; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D051381:Rats
D002352:Carrier Proteins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D026901:Membrane Transport Proteins; C020723:citrate-binding transport protein; D019343:Citric Acid; D000105:Acetyl Coenzyme A