Structure, function and regulation of the tricarboxylate transport protein from rat liver mitochondria.
Recent progress is summarized on the structure, function, and regulation of the tricarboxylate (i.e., citrate) transport protein (CTP) from the rat liver mitochondrial inner membrane. The transporter has been purified and its reconstituted function characterized. A cDNA clone encoding the CTP has been isolated and sequenced, thus enabling a deduction of the complete amino acid sequence of this 32.6 kDa transport protein. Dot matrix analysis and sequence alignment indicate that based on structural considerations the CTP can be assigned to the mitochondrial carrier family. Hydropathy analysis of the transporter sequence indicates six putative membrane-spanning alpha-helices and has permitted the development of an initial model for the topography of the CTP within the inner membrane. The questions as to whether more than one gene encodes the CTP and whether more than one isoform is expressed remain unanswered at this time. Studies documenting a diabetes-induced alteration in the function of several mitochondrial anion transporters, which can be reversed by treatment with insulin, provide a physiologically/pathologically relevant experimental system for studying the molecular mechanism(s) by which mitochondrial transporters are regulated. Potential future research directions are discussed.
Kaplan
R S
RS
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile 36688.
Mayor
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002417:Cattle; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D005796:Genes; D007425:Intracellular Membranes / Q000378:metabolism; D008930:Mitochondria, Liver / Q000737:chemistry*; D008954:Models, Biological; D008969:Molecular Sequence Data; D051381:Rats
D002352:Carrier Proteins; D018076:DNA, Complementary; C020723:citrate-binding transport protein