The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface

Xu, Ningyi; Zhang, Shaobing O.; Cole, Ronald A.; McKinney, Sean A.; Guo, Fei; Haas, Joel T.; Bobba, Sudheer; Farese, Robert V.; Mak, Ho Yi

doi:10.1083/jcb.201201139

Cited by 247 publications

(223 citation statements)

References 61 publications

(107 reference statements)

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“…The reduction of PC levels in the asm-3(ok1744) mutant embryos was remarkable because a decrease of this lipid class increases the size of the lipid droplets in the intestine of adult worms (Krahmer et al 2011;Xu et al 2012;Ehmke et al 2014). This also could be the reason for lipid droplet enlargement in the asm-3 mutant embryos.…”

Section: Discussionmentioning

confidence: 97%

Genetics of Lipid-Storage Management inCaenorhabditis elegansEmbryos

et al. 2016

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Lipids play a pivotal role in embryogenesis as structural components of cellular membranes, as a source of energy, and as signaling molecules. On the basis of a collection of temperature-sensitive embryonic lethal mutants, a systematic database search, and a subsequent microscopic analysis of .300 interference RNA (RNAi)-treated/mutant worms, we identified a couple of evolutionary conserved genes associated with lipid storage in Caenorhabditis elegans embryos. The genes include cpl-1 (cathepsin L-like cysteine protease), ccz-1 (guanine nucleotide exchange factor subunit), and asm-3 (acid sphingomyelinase), which is closely related to the human Niemann-Pick disease-causing gene SMPD1. The respective mutant embryos accumulate enlarged droplets of neutral lipids (cpl-1) and yolk-containing lipid droplets (ccz-1) or have larger genuine lipid droplets (asm-3). The asm-3 mutant embryos additionally showed an enhanced resistance against C band ultraviolet (UV-C) light. Herein we propose that cpl-1, ccz-1, and asm-3 are genes required for the processing of lipid-containing droplets in C. elegans embryos. Owing to the high levels of conservation, the identified genes are also useful in studies of embryonic lipid storage in other organisms.

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Section: Discussionmentioning

confidence: 97%

Genetics of Lipid-Storage Management inCaenorhabditis elegansEmbryos

et al. 2016

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“…Furthermore, DGAT2 appears to be part of a large heterologous protein complex (Ͼ650 kDa) as co-immunoprecipitation experiments have shown that DGAT2 can interact with two proteins, FATP1 and SCD1 (9,23,24). Both of these enzymes catalyze the synthesis of substrates utilized by DGAT2 for TG synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Both of these enzymes catalyze the synthesis of substrates utilized by DGAT2 for TG synthesis. FATP1 possesses acyl CoA synthetase activity and activates fatty acids for DGAT2 (24,39). SCD1 converts saturated fatty acyl CoAs to monounsaturated acyl CoAs which are abundant in TG (40).…”

Section: Discussionmentioning

confidence: 99%

“…CoA desaturase (SCD)-1 and fatty acid transport protein (FATP)-1 are two enzymes that produce substrates (fatty acyl CoA) for DGAT enzymes and have been shown to interact with DGAT2 (23,24). We sought to determine if DGAT2 interacts with the enzymes that produce 1,2-diacylglycerol, such as phosphatidate phosphatase/lipin and/or MGAT2.…”

Section: Mgat2 Interacts With Dgat2-stearoylmentioning

confidence: 99%

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Diacylglycerol Acyltransferase-2 (DGAT2) and Monoacylglycerol Acyltransferase-2 (MGAT2) Interact to Promote Triacylglycerol Synthesis

Jin

McFie

Banman

et al. 2014

Journal of Biological Chemistry

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Background: DGAT2 catalyzes the final and committed step of triacylglycerol (TG) biosynthesis. Results: Co-immunoprecipitation experiments and in situ proximity ligation assays showed that DGAT2 and MGAT2 interact. Conclusion: DGAT2 can utilize diacylglycerol generated by MGAT2 for TG synthesis. Significance: These findings provide insight into the spatial arrangement of enzymes involved in triacylglycerol biosynthesis.

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“…They are surrounded by a PL monolayer mainly containing PC and PE (Bartz et al 2007). Because the ratio between TAG and PC could be an important determinant of LD size (Krahmer et al 2011;McFie et al 2011;Xu et al 2012), LDs were visualized in the sams-1 mutants through 3D fluorescence imaging. Adult sams-1 mutants formed enlarged intestinal LDs that dramatically differed from those observed in wild-type worms (Fig.…”

Section: Sams-1 Mutants Exhibit Enlarged Lipid Droplets Throughout Thmentioning

confidence: 99%

S-Adenosyl methionine synthetase 1 limits fat storage in Caenorhabditis elegans

Ehmke¹,

Luthe

Schnabel

et al. 2014

Genes Nutr

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Cytosolic lipid droplets are versatile, evolutionarily conserved organelles that are important for the storage and utilization of lipids in almost all cell types. To obtain insight into the physiological importance of lipid droplet size, we isolated and characterized a new S-adenosyl methionine synthetase 1 (SAMS-1)-deficient Caenorhabditis elegans mutant, which have enlarged lipid droplets throughout its life cycle. We found that the sams-1 mutant showed a markedly reduced body size and progeny number; impaired synthesis of phosphatidylcholine, a major membrane phospholipid; and elevated expression of key lipogenic genes, such as dgat-2, resulting in the accumulation of triacylglyceride in fewer, but larger, lipid droplets. The sams-1 mutant store more than 50 % (wild type: 10 %) of its intestinal fat in large lipid droplets, C10 lm 3 in size. In response to starvation, SAMS-1 deficiency causes reduced depletion of a subset of lipid droplets located in the anterior intestine. Given the importance of liberation of fatty acids from lipid droplets, we propose that the physiological function of SAMS-1, a highly conserved enzyme involved in one-carbon metabolism, is the limitation of fat storage to ensure proper growth and reproduction.

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The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface

Abstract: A complex between the ER resident protein FATP1 and the lipid droplet–localized DGAT2 protein facilitates lipid droplet expansion in C. elegans and mammalian cells.

Cited by 247 publications

References 61 publications

Genetics of Lipid-Storage Management inCaenorhabditis elegansEmbryos

Genetics of Lipid-Storage Management inCaenorhabditis elegansEmbryos

Diacylglycerol Acyltransferase-2 (DGAT2) and Monoacylglycerol Acyltransferase-2 (MGAT2) Interact to Promote Triacylglycerol Synthesis

S-Adenosyl methionine synthetase 1 limits fat storage in Caenorhabditis elegans

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