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Protein mediated fatty acid uptake: Synergy between CD36/FAT-facilitated transport and acyl-CoA synthetase-driven metabolism

Published on Mar 1, 2014in Archives of Biochemistry and Biophysics3.559
· DOI :10.1016/j.abb.2014.01.025
Hannah Schneider2
Estimated H-index: 2
(Heidelberg University),
Sarah Staudacher2
Estimated H-index: 2
(Heidelberg University)
+ 3 AuthorsJoachim Füllekrug28
Estimated H-index: 28
(Heidelberg University)
Abstract
The mechanism of cellular fatty acid uptake is highly relevant for basic and clinical research. Previous work has demonstrated that fatty acid uptake is facilitated by cell surface membrane proteins as well as by intracellularly localized enzymes. Here, the exogenous expression of the CD36/FAT glycoprotein and the acyl-CoA synthetases FATP4 and ACSL1 in MDCK cells was quantified by comparison to recombinant proteins, and related to the corresponding increases of fatty acid uptake. At the molecular level, CD36/FAT was 30-fold more efficient than either FATP4 or ACSL1 in enhancing fatty acid uptake. Remarkably, co-expression of CD36/FAT with FATP4 or ACSL1 led to a higher increase of fatty acid uptake than expected from the combined individual contributions, whereas co-expression of FATP4 and ACSL1 did not. Immunofluorescence microscopy confirmed the plasma membrane localization of CD36/FAT and the intracellular localization of FATP4 to the endoplasmic reticulum, and of ACSL1 to mitochondria. Concluding, we suggest that fatty acid uptake in our model system is organized by two spatially distinct but synergistic mechanisms: the cell surface protein CD36/FAT directly facilitates fatty acid transport across the plasma membrane, whereas the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping.
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