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

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,...

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Bibliographic Details
Published in:Molecular biology of the cell 2015-06, Vol.26 (12), p.2333-2342
Main Authors: Suzuki, Michitaka, Murakami, Tatsuro, Cheng, Jinglei, Kano, Hiroyuki, Fukata, Masaki, Fujimoto, Toyoshi
Format: Article
Language:English
Subjects:
Adipocytes - enzymology
Adipocytes - metabolism
ADP-Ribosylation Factor 1 - metabolism
Coat Protein Complex I - metabolism
Cytoskeletal Proteins - metabolism
Gene Expression Regulation
Humans
Lipase - genetics
Lipase - metabolism
Lipid Droplets - metabolism
Lipoylation
Triglycerides - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E14-11-1504