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FAT/CD36 is located on the outer mitochondrial membrane, upstream of long chain acyl-CoA synthetase, and regulates palmitate oxidation.
MedLine Citation:
PMID:  21463259     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
FAT/CD36, 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. We demonstrate, using several different approaches, that in skeletal muscle FAT/CD36 resides on the outer mitochondrial membrane (OMM). To determine the functional role of mitochondrial FAT/CD36 in this tissue we determined oxygen consumption rates in permeabilized muscle fibers in wild-type and FAT/CD36 KO mice using a variety of substrates. Despite comparable muscle mitochondrial content, as assessed by unaltered mtDNA, citrate synthase, b-hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase complex IV and respiratory capacities (maximal OXPHOS respiration) in WT and KO mice, palmitate supported respiration was 34% lower in KO animals. In contrast, palmitoyl-CoA supported respiration was unchanged. These data 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:
Brennan K Smith; Swati S Jain; Stephanie Rimbaud; Aaron Dam; Joe Quadrilatero; Renee Ventura-Clapier; Arend Bonen; Graham P Holloway
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-4
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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