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Mol Biol Cell. 2015 Jun 15;26(12):2333-42. doi: 10.1091/mbc.E14-11-1504. Epub 2015 Apr 22.

ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

Author information

1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
2
Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki 444-8787, Japan Department of Physiological Sciences, School of Life Science, SOKENDAI (Graduate University for Advanced Studies), Okazaki 444-8787, Japan.
3
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan tfujimot@med.nagoya-u.ac.jp.

Abstract

Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs.

PMID:
25904333
PMCID:
PMC4462949
DOI:
10.1091/mbc.E14-11-1504
[Indexed for MEDLINE]
Free PMC Article

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