title: Nutritional and Hormonal Regulation of Citrate and Carnitine/Acylcarnitine Transporters: Two Mitochondrial Carriers Involved in Fatty Acid Metabolism.
abstract: The transport of solutes across the inner mitochondrial membrane is catalyzed by a family of nuclear-encoded membrane-embedded proteins called mitochondrial carriers (MCs). The citrate carrier (CiC) and the carnitine/acylcarnitine transporter (CACT) are two members of the MCs family involved in fatty acid metabolism. By conveying acetyl-coenzyme A, in the form of citrate, from the mitochondria to the cytosol, CiC contributes to fatty acid and cholesterol synthesis; CACT allows fatty acid oxidation, transporting cytosolic fatty acids, in the form of acylcarnitines, into the mitochondrial matrix. Fatty acid synthesis and oxidation are inversely regulated so that when fatty acid synthesis is activated, the catabolism of fatty acids is turned-off. Malonyl-CoA, produced by acetyl-coenzyme A carboxylase, a key enzyme of cytosolic fatty acid synthesis, represents a regulator of both metabolic pathways. CiC and CACT activity and expression are regulated by different nutritional and hormonal conditions. Defects in the corresponding genes have been directly linked to various human diseases. This review will assess the current understanding of CiC and CACT regulation; underlining their roles in physio-pathological conditions. Emphasis will be placed on the molecular basis of the regulation of CiC and CACT associated with fatty acid metabolism.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy. anna.giudetti@unisalento.it.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Giudetti
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy. eleonora.stanca@unisalento.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Stanca
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy. luisa.siculella@unisalento.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy. gabriele.gnoni@unisalento.it.
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Gnoni
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy. fabrizio.damiano@unisalento.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Damiano
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002333:Carnitine Acyltransferases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050155:Lipogenesis; D008928:Mitochondria / Q000378:metabolism; D013963:Thyroid Hormones / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D005227:Fatty Acids; D013963:Thyroid Hormones; C020723:citrate-binding transport protein; D000105:Acetyl Coenzyme A; D002784:Cholesterol; D002333:Carnitine Acyltransferases
keywords: carnitine/acylcarnitine translocase; citrate carrier; fatty acid synthesis; hormonal regulation; nutritional regulation; β-oxidation