Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient.

The carnitine-acylcarnitine carrier (CAC) catalyzes the translocation of long-chain fatty acids across the inner mitochondrial membrane. We cloned and sequenced the human CAC cDNA, which has an open reading frame of 903 nucleotides. Northern blot studies revealed different expression levels of CAC in various human tissues. Furthermore, mutation analysis was performed for a CAC-deficient infant. Direct sequencing of the patient's cDNA revealed a homozygous cytosine nucleotide insertion. This insertion provokes a frameshift and an extension of the open reading frame with 23 novel codons. This is the first report documenting a mutation, in the CAC cDNA, responsible for mitochondrial beta-oxidation impairment.

[1]  F RANKLIN H. E PSTEIN,et al.  Mechanisms of Disease Mechanisms of Disease a Therosclerosis — a N I Nflammatory D Isease a Factors That Induce and Promote Inflammation or Atherogenesis , 2022 .

[2]  V. Iacobazzi,et al.  The mitochondrial carnitine carrier protein: cDNA cloning, primary structure and comparison with other mitochondrial transport proteins. , 1997, The Biochemical journal.

[3]  V. Iacobazzi,et al.  Organization and sequence of the human gene for the mitochondrial citrate transport protein. , 1997, DNA sequence : the journal of DNA sequencing and mapping.

[4]  J. Walker,et al.  Identification by bacterial expression and functional reconstitution of the yeast genomic sequence encoding the mitochondrial dicarboxylate carrier protein , 1996, FEBS letters.

[5]  M. De Rijcke,et al.  The ARG11 Gene of Saccharomyces cerevisiae Encodes a Mitochondrial Integral Membrane Protein Required for Arginine Biosynthesis* , 1996, The Journal of Biological Chemistry.

[6]  D. Turnbull,et al.  Neonatal hyperammonemia caused by a defect of carnitine-acylcarnitine translocase. , 1995, The Journal of pediatrics.

[7]  F. Palmieri,et al.  Probing the Active Site of the Reconstituted Carnitine Carrier from Rat Liver Mitochondria with Sulfhydryl Reagents , 1995 .

[8]  F. Palmieri,et al.  Probing the active site of the reconstituted carnitine carrier from rat liver mitochondria with sulfhydryl reagents. A cysteine residue is localized in or near the substrate binding site. , 1995, European journal of biochemistry.

[9]  M. S. Murthy,et al.  Carnitine-acylcarnitine translocase deficiency: implications in human pathology. , 1994, Biochimica et biophysica acta.

[10]  F. Palmieri.  Mitochondrial carrier proteins , 1994, FEBS letters.

[11]  J. Walker,et al.  The sequences of human and bovine genes of the phosphate carrier from mitochondria contain evidence of alternatively spliced forms. , 1994, The Journal of biological chemistry.

[12]  F. Palmieri,et al.  The reconstituted carnitine carrier from rat liver mitochondria: evidence for a transport mechanism different from that of the other mitochondrial translocators. , 1994, Biochimica et biophysica acta.

[13]  A. Messina,et al.  Cloning and sequencing of the rat cDNA encoding the mitochondrial 2-oxoglutarate carrier protein. , 1994, DNA sequence : the journal of DNA sequencing and mapping.

[14]  M. Runswick,et al.  The mitochondrial transport protein superfamily , 1993, Journal of bioenergetics and biomembranes.

[15]  D. Wood,et al.  The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure, and comparison with other mitochondrial transport proteins. , 1993, The Journal of biological chemistry.

[16]  S. Pande,et al.  Carnitine-acylcarnitine translocase deficiency with severe hypoglycemia and auriculo ventricular block. Translocase assay in permeabilized fibroblasts. , 1993, The Journal of clinical investigation.

[17]  T. Dierks,et al.  The mitochondrial carnitine carrier: characterization of SH-groups relevant for its transport function. , 1992, Biochimica et biophysica acta.

[18]  P. Coates,et al.  Molecular basis of mitochondrial fatty acid oxidation defects. , 1992, Journal of lipid research.

[19]  C. Stanley,et al.  Brief report: a deficiency of carnitine-acylcarnitine translocase in the inner mitochondrial membrane. , 1992, The New England journal of medicine.

[20]  J. Walker,et al.  Sequences of the human and bovine genes for the mitochondrial 2-oxoglutarate carrier. , 1992, DNA sequence : the journal of DNA sequencing and mapping.

[21]  F. Palmieri,et al.  Characterization of the unidirectional transport of carnitine catalyzed by the reconstituted carnitine carrier from rat liver mitochondria. , 1991, Biochimica et biophysica acta.

[22]  J. Mattick,et al.  'Touchdown' PCR to circumvent spurious priming during gene amplification. , 1991, Nucleic acids research.

[23]  F. Palmieri,et al.  Kinetic characterization of the reconstituted carnitine carrier from rat liver mitochondria. , 1991, Biochimica et biophysica acta.

[24]  F. Palmieri,et al.  Identification and purification of the carnitine carrier from rat liver mitochondria. , 1990, Biochimica et biophysica acta.

[25]  P. Pedersen,et al.  Energy-linked anion transport. Cloning, sequencing, and characterization of a full length cDNA encoding the rat liver mitochondrial proton/phosphate symporter. , 1989, The Journal of biological chemistry.

[26]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[27]  C. Stanley.  New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. , 1987, Advances in pediatrics.

[28]  M. S. Murthy,et al.  Mechanism of carnitine acylcarnitine translocase-catalyzed import of acylcarnitines into mitochondria. , 1984, The Journal of biological chemistry.

[29]  J. A. Idell-Wenger.  Carnitine:acylcarnitine translocase of rat heart mitochondria. Competition for carnitine uptake by carnitine esters. , 1981, The Journal of biological chemistry.

[30]  S. Pande,et al.  Carnitine-acylcarnitine translocase catalyzes an equilibrating unidirectional transport as well. , 1980, The Journal of biological chemistry.

[31]  R. Ramsay,et al.  The mechanism of fatty acid uptake by heart mitochondria: An acylcarnitine‐carnitine exchange , 1975, FEBS letters.

[32]  S. Pande.  A mitochondrial carnitine acylcarnitine translocase system. , 1975, Proceedings of the National Academy of Sciences of the United States of America.