title: Carnitine palmitoyltransferase 1C: From cognition to cancer.
abstract: Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression. Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with l-carnitine and acyl-CoA esters. The lack of an easily measurable biological activity has hampered attempts to elucidate the cellular and physiological role of CPT1C but has not diminished the interest of the biomedical research community in this CPT1 isoform. The observations that CPT1C binds malonyl-CoA and long-chain acyl-CoA suggest that it is a sensor of lipid metabolism in neurons, where it appears to impact ceramide and triacylglycerol (TAG) metabolism. CPT1C global knock-out mice show a wide range of brain disorders, including impaired cognition and spatial learning, motor deficits, and a deregulation in food intake and energy homeostasis. The first disease-causing CPT1C mutation was recently described in humans, with Cpt1c being identified as the gene causing hereditary spastic paraplegia. The putative role of CPT1C in the regulation of complex-lipid metabolism is supported by the observation that it is highly expressed in certain virulent tumor cells, conferring them resistance to glucose- and oxygen-deprivation. Therefore, CPT1C may be a promising target in the treatment of cancer. Here we review the molecular, biochemical, and structural properties of CPT1C and discuss its potential roles in brain function, and cancer.
authors.affiliation: CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallés, Barcelona, Spain. Electronic address: ncasals@uic.es.
authors.forename: Núria
authors.initials: N
authors.lastname: Casals
authors.affiliation: Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry KA4 7AL, UK. Electronic address: V.A.Zammit@warwick.ac.uk.
authors.forename: Victor
authors.initials: V
authors.lastname: Zammit
authors.affiliation: CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Herrero
authors.affiliation: CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallés, Barcelona, Spain.
authors.forename: Rut
authors.initials: R
authors.lastname: Fadó
authors.affiliation: CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallés, Barcelona, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Rodríguez-Rodríguez
authors.affiliation: CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028 Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Serra
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000502:physiology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000201:enzymology; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D009369:Neoplasms / Q000201:enzymology*
chemical_list: C542591:CPT1B protein, human; D002334:Carnitine O-Palmitoyltransferase
keywords: Cancer; Carnitine palmitoyltransferase 1C; Cognition; Energy homeostasis; Hereditary spastic paraplegia; Lipid metabolism