title: Fatty acid binding protein facilitates sarcolemmal fatty acid transport but not mitochondrial oxidation in rat and human skeletal muscle.
abstract: The transport of long-chain fatty acids (LCFAs) across mitochondrial membranes is regulated by carnitine palmitoyltransferase I (CPTI) activity. However, it appears that additional fatty acid transport proteins, such as fatty acid translocase (FAT)/CD36, influence not only LCFA transport across the plasma membrane, but also LCFA transport into mitochondria. Plasma membrane-associated fatty acid binding protein (FABPpm) is also known to be involved in sacrolemmal LCFA transport, and it is also present on the mitochondria. At this location, it has been identified as mitochondrial aspartate amino transferase (mAspAT), despite being structurally identical to FABPpm. Whether this protein is also involved in mitochondrial LCFA transport and oxidation remains unknown. Therefore, we have examined the ability of FABPpm/mAspAT to alter mitochondrial fatty acid oxidation. Muscle contraction increased (P < 0.05) the mitochondrial FAT/CD36 content in rat (+22%) and human skeletal muscle (+33%). By contrast, muscle contraction did not alter the content of mitochondrial FABPpm/mAspAT protein in either rat or human muscles. Electrotransfecting rat soleus muscles, in vivo, with FABPpm cDNA increased FABPpm protein in whole muscle (+150%; P < 0.05), at the plasma membrane (+117%; P < 0.05) and in mitochondria (+80%; P < 0.05). In these FABPpm-transfected muscles, palmitate transport into giant vesicles was increased by +73% (P < 0.05), and fatty acid oxidation in intact muscle was increased by +18% (P < 0.05). By contrast, despite the marked increase in mitochondrial FABPpm/mAspAT protein content (+80%), the rate of mitochondrial palmitate oxidation was not altered (P > 0.05). However, electrotransfection increased mAspAT activity by +70% (P < 0.05), and the mitochondrial FABPpm/mAspAT protein content was significantly correlated with mAspAT activity (r = 0.75). It is concluded that FABPpm has two distinct functions depending on its subcellular location: (a) it contributes to increasing sarcolemmal LCFA transport while not contributing directly to LCFA transport into mitochondria; and (b) its primary role at the mitochondria level is to transport reducing equivalents into the matrix.
authors.affiliation: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Canada, N1G 2W1. ghollowa@uoguelph.ca
authors.forename: Graham P
authors.initials: GP
authors.lastname: Holloway
authors.forename: Jamie
authors.initials: J
authors.lastname: Lally
authors.forename: James G
authors.initials: JG
authors.lastname: Nickerson
authors.forename: Hakam
authors.initials: H
authors.lastname: Alkhateeb
authors.forename: Laelie A
authors.initials: LA
authors.lastname: Snook
authors.forename: George J F
authors.initials: GJ
authors.lastname: Heigenhauser
authors.forename: Jorge
authors.initials: J
authors.lastname: Calles-Escandon
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Spriet
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
mesh_terms: D000328:Adult; D000818:Animals; D024442:Aspartate Aminotransferase, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism*; D014162:Transfection
chemical_list: D018955:CD36 Antigens; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; C515999:Got2 protein, rat; D019308:Palmitic Acid; D024442:Aspartate Aminotransferase, Mitochondrial