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FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation.
Biochem J. 2011 Jul 01; 437(1):125-34.BJ

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+Show Affiliations

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21463259

Citation

Smith, Brennan K., et al. "FAT/CD36 Is Located On the Outer Mitochondrial Membrane, Upstream of Long-chain acyl-CoA Synthetase, and Regulates Palmitate Oxidation." The Biochemical Journal, vol. 437, no. 1, 2011, pp. 125-34.
Smith BK, Jain SS, Rimbaud S, et al. FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. Biochem J. 2011;437(1):125-34.
Smith, B. K., Jain, S. S., Rimbaud, S., Dam, A., Quadrilatero, J., Ventura-Clapier, R., Bonen, A., & Holloway, G. P. (2011). FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. The Biochemical Journal, 437(1), 125-34. https://doi.org/10.1042/BJ20101861
Smith BK, et al. FAT/CD36 Is Located On the Outer Mitochondrial Membrane, Upstream of Long-chain acyl-CoA Synthetase, and Regulates Palmitate Oxidation. Biochem J. 2011 Jul 1;437(1):125-34. PubMed PMID: 21463259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. AU - Smith,Brennan K, AU - Jain,Swati S, AU - Rimbaud,Stéphanie, AU - Dam,Aaron, AU - Quadrilatero,Joe, AU - Ventura-Clapier,Renée, AU - Bonen,Arend, AU - Holloway,Graham P, PY - 2011/4/6/entrez PY - 2011/4/6/pubmed PY - 2011/8/31/medline SP - 125 EP - 34 JF - The Biochemical journal JO - Biochem. J. VL - 437 IS - 1 N2 - 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. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/21463259/FAT/CD36_is_located_on_the_outer_mitochondrial_membrane_upstream_of_long_chain_acyl_CoA_synthetase_and_regulates_palmitate_oxidation_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20101861 DB - PRIME DP - Unbound Medicine ER -