title: [Carnitine - mitochondria and beyond].
abstract: Carnitine [(3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate] in mammals is mainly delivered with diet. It enters the cell due to the activity of organic cation/carnitine transporter OCTN2 (SLC22A5), it can be as well transported by CT2 (SLC22A16) and a transporter of neutral and basic amino acids ATB0, +(SLC6A14). The hydroxyl group of carnitine is able to form esters with organic acids (xenobiotics, fatty acids) due to the activity of acylcarnitine transferases. Carnitine is necessary for transfer of fatty acids to mitochondria: in functioning of the so-called carnitine shuttle an essential role is fulfilled by palmitoylcarnitine transferase 1, carnitine carrier (SLC25A20) in the inner mitochondrial membrane and palmitoylcarnitine transferase 2. Oxidation of fatty acids takes also place in peroxisomes. The produced medium-chain acyl derivatives are exported as acylcarnitines, most probably by OCTN3 (Slc22a21). It has been postulated that acylcarnitines can cross the outer mitochondrial membrane through the voltage-dependent anion channel (VDAC) and/or through the palmitoycarnitine transferase 1 oligomer. Mutations of genes coding carnitine plasma membrane transporters result in the primary carnitine deficiency, with symptoms affecting normal functioning of muscles (including heart) and brain. Mechanisms regulating functioning of these transporters have been presented with emphasis on their role as potential therapeutic targets.
authors.affiliation: Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Nałęcz
authors.affiliation: Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland.
authors.forename: Maciej J
authors.initials: MJ
authors.lastname: Nałęcz
mesh_terms: D000818:Animals; D001692:Biological Transport; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism; D002331:Carnitine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5 / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D027701:Organic Cation Transport Proteins; C467737:SLC22A16 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine
keywords: OCTN; carnitine; mitochondria; peroxisomes