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.
Gnoni
Gabriele V
GV
Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Science and Technologies, University of Salento, 73100 Lecce, Italy. gabriele.gnoni@unisalento.it
Priore
Paola
P
Geelen
Math J H
MJ
Siculella
Luisa
L
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