title: FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation.
abstract: FAT/CD36 (fatty acid translocase/Cluster of Differentiation 36), a plasma membrane fatty-acid transport protein, has been found on mitochondrial membranes; however, it remains unclear where FAT/CD36 resides on this organelle or its functional role within mitochondria. In the present study, we demonstrate, using several different approaches, that in skeletal muscle FAT/CD36 resides on the OMM (outer mitochondrial membrane). To determine the functional role of mitochondrial FAT/CD36 in this tissue, we determined oxygen consumption rates in permeabilized muscle fibres in WT (wild-type) and FAT/CD36-KO (knockout) mice using a variety of substrates. Despite comparable muscle mitochondrial content, as assessed by unaltered mtDNA (mitochondrial DNA), citrate synthase, β-hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase complex IV and respiratory capacities [maximal OXPHOS (oxidative phosphorylation) respiration] in WT and KO mice, palmitate-supported respiration was 34% lower in KO animals. In contrast, palmitoyl-CoA-supported respiration was unchanged. These results indicate that FAT/CD36 is key for palmitate-supported respiration. Therefore we propose a working model of mitochondrial fatty-acid transport, in which FAT/CD36 is positioned on the OMM, upstream of long-chain acyl-CoA synthetase, thereby contributing to the regulation of mitochondrial fatty-acid transport. We further support this model by providing evidence that FAT/CD36 is not located in mitochondrial contact sites, and therefore does not directly interact with carnitine palmitoyltransferase-I as original proposed.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1.
authors.forename: Brennan K
authors.initials: BK
authors.lastname: Smith
authors.forename: Swati S
authors.initials: SS
authors.lastname: Jain
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rimbaud
authors.forename: Aaron
authors.initials: A
authors.lastname: Dam
authors.forename: Joe
authors.initials: J
authors.lastname: Quadrilatero
authors.forename: Renée
authors.initials: R
authors.lastname: Ventura-Clapier
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
authors.forename: Graham P
authors.initials: GP
authors.lastname: Holloway
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D051336:Mitochondrial Membranes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism*; D051381:Rats
chemical_list: D000214:Acyl Coenzyme A; D018955:CD36 Antigens; D010168:Palmitates; D003066:Coenzyme A Ligases