| FAT/CD36 is located on the outer mitochondrial membrane, upstream of long chain acyl-CoA synthetase, and regulates palmitate oxidation. | |
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MedLine Citation:
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PMID: 21463259 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-4-4 |
Journal Detail:
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Title: The Biochemical journal Volume: - ISSN: 1470-8728 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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