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Targeting of acyl‐CoA synthetase 3 to lipid droplets
Author(s) -
Fuellekrug Joachim,
Grossmann Regina,
Rudolph Berenice,
Becker Melanie,
Thiele Christoph,
Stremmel Wolfgang,
Ehehalt Robert,
Digel Margarete
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.845.3
Subject(s) - lipid droplet , organelle , phospholipid , lipid microdomain , biochemistry , lipid metabolism , biology , microbiology and biotechnology , perilipin , lipid bilayer , chemistry , membrane , adipocyte , adipose tissue
Lipid droplets emerge as dynamic organelles highly relevant for lipid homeostasis and the pathophysiology of metabolic diseases. We are using fatty acyl‐CoA synthetases (ACS), especially ACSL3 as a paradigm to investigate the formation and growth of lipid droplets. Out of eleven mammalian long chain ACS, ACSL3 is the only family member localizing specifically to lipid droplets and the ER. The distribution of ACSL3 between these two organelles depends on the cell type and whether exogenous fatty acids are being supplied. The N‐terminal region of ACSL3 is sufficient to direct reporter proteins to lipid droplets which we analysed by confocal microscopy. Mutational analysis demonstrated that only amino acids 12 to 51 are essential for targeting. ACSL3 is tightly membrane associated by an amphipathic helix contained within the N‐terminal sorting signal. During lipid droplet biogenesis, ACSL3 moves from the bilayer membrane of the ER to the phospholipid monolayer of nascent lipid droplets as we demonstrated by live microscopy. Overexpression of ACSL3 results not only in increased cellular enzyme activity but also in the enhanced uptake of exogenous fatty acids. This suggests that ACSL3 is functionally relevant for the regulation of fatty acid uptake. Moreover, we speculate that the specific localization of ACSL3 is important for the local biosynthesis of phospholipids at the surface of the lipid droplets.