Energetics Underlying the Process of Long-Chain Fatty Acid Transport

Azizan, A.; Sherin, David; DiRusso, Concetta C.; Black, Paul N.

doi:10.1006/abbi.1999.1171

Cited by 22 publications

(24 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are consistent with the hypothesis that transport of LCFAs into mammalian cells is coupled to esterification of imported LCFAs at the inner leaflet of the plasma membrane. This proposed mechanism is analogous to the well characterized fatty acid transport system in Escherichia coli (13), in which the outer membrane protein, FadL, binds and transports LCFAs. Imported substrates are esterified upon transport across the inner membrane by a membrane-associated acyl-CoA synthetase, FadD.…”

mentioning

confidence: 84%

Membrane Topology of the Murine Fatty Acid Transport Protein 1

Lewis

Listenberger

Ory

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The murine fatty acid transport protein (FATP1) was identified in an expression cloning screen for proteins that facilitate transport of fatty acids across the plasma membranes of mammalian cells. Hydropathy analysis of this protein suggests a model in which FATP1 has multiple membrane-spanning domains. To test this model, we inserted a hemagglutinin epitope tag at the amino terminus or a FLAG tag at the carboxyl terminus of the FATP1 cDNA and expressed these constructs in NIH 3T3 cells. Both tagged constructs produce proteins of the expected molecular masses and are functional in fatty acid import assays. Indirect immunofluorescence studies with selective permeabilization conditions and protease protection studies of sealed membrane vesicles from cells expressing epitope-tagged FATP1 were performed. These experiments show that the extreme amino terminus of tagged FATP1 is oriented toward the extracellular space, whereas the carboxyl terminus faces the cytosol. Additionally, enhanced green fluorescent protein fusion constructs containing predicted membrane-associated or soluble portions of FATP1 were expressed in Cos7 cells and analyzed by immunofluorescence and subcellular fractionation. These experiments demonstrate that amino acids 1-51, 52-100, and 101-190 contain signals for integral association with the membrane, whereas residues 258 -313 and 314 -475 are only peripherally membrane-associated. Amino acid residues 191-257 and 476 -646 do not direct membrane association and likely face the cytosol. Taken together, these data support a model of FATP1 as a polytopic membrane protein with at least one transmembrane and multiple membrane-associated domains. This study provides the first experimental evidence for topology of a member of the family of plasma membrane fatty acid transport proteins.

show abstract

mentioning

confidence: 84%

Membrane Topology of the Murine Fatty Acid Transport Protein 1

Lewis

Listenberger

Ory

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The concept of vectorial acylation has been put forward as a model for long-chain fatty acid uptake in bacteria (Azizan et al, 1999;Klein et al, 1971). There, the bacterial fatty acid transporter FadL in the outer membrane works in concert with the inner-membrane-associated fatty acyl-CoA synthetase FadD.…”

Section: Journal Of Cell Science 119 (22)mentioning

confidence: 99%

Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4

Milger

Herrmann

Becker

et al. 2006

Journal of Cell Science

202

210

View full text Add to dashboard Cite

Long-chain fatty acids are important metabolites for the generation of energy and the biosynthesis of lipids. The molecular mechanism of their cellular uptake has remained controversial. The fatty acid transport protein (FATP) family has been named according to its proposed function in mediating this process at the plasma membrane. Here, we show that FATP4 is in fact localized to the endoplasmic reticulum and not the plasma membrane as reported previously. Quantitative analysis confirms the positive correlation between expression of FATP4 and uptake of fatty acids. However, this is dependent on the enzymatic activity of FATP4, catalyzing the esterification of fatty acids with CoA. Monitoring fatty acid uptake at the single-cell level demonstrates that the ER localization of FATP4 is sufficient to drive transport of fatty acids. Expression of a mitochondrial acyl-CoA synthetase also enhances fatty acid uptake, suggesting a general relevance for this mechanism. Our results imply that cellular uptake of fatty acids can be regulated by intracellular acyl-CoA synthetases. We propose that the enzyme FATP4 drives fatty acid uptake indirectly by esterification. It is not a transporter protein involved in fatty acid translocation at the plasma membrane.

show abstract

“…Hamilton and colleagues (34) have suggested uncharged fatty acids bind to and flip rapidly between the two membrane surfaces; thus the normal chemical milieu of the periplasmic space may promote the formation of uncharged fatty acid molecules that readily partition into and flip to the cytosolic face of the membrane. The disruption of the periplasmic space upon osmotic shock will increase pH, which is likely to reduce the number of protonated fatty acids and depress the rate of fatty acid transport (32).…”

Section: Minireview: Bacterial Long Chain Fatty Acid Transport 49564mentioning

confidence: 99%

“…In essence, this ACSL functions to abstract and activate exogenous LCFAs concomitant with transport across the inner membrane. Both CoA and ATP pools are required for fatty acid transport, which reflects the requirement for these substrates by FadD for activity (32,36). A number of the initial studies describing the E. coli ACSL noted this enzyme was found both within the inner membrane and cytosol, suggesting it moved between different cellular compartments during its catalytic cycle.…”

Section: Fatty Acid Transport Across Inner Membrane Andmentioning

confidence: 99%