α/β Hydrolase Domain-containing Protein 1 Acts As a Lysolipid Lipase and is Involved in Lipid Droplet Formation

Overview

Journal Natl Sci Rev

Date 2025 Jan 10

PMID 39791125

Authors

Ismael Torres-Romero

Bertrand Legeret

Marie Bertrand

Damien Sorigue

Alicia Damm

Stephan Cuine

Florian Veillet

Carla Blot

Sabine Brugiere

Yohann Coute

Matthew G Garneau

Hari K Kotapati

Yi Xin

Jian Xu

Philip D Bates

Abdou R Thiam

Fred Beisson

Yonghua Li-Beisson

Affiliations

Soon will be listed here.

Abstract

Lipid droplets (LDs) are the major sites of lipid and energy homeostasis. However, few LD biogenesis proteins have been identified. Using model microalga , we show that ABHD1, an α/β-hydrolase domain-containing protein, is localized to the LD surface and stimulates LD formation through two actions: one enzymatic and one structural. The knockout mutants contained similar amounts of triacylglycerols (TAG) but their LDs showed a higher content of lyso-derivatives of betaine lipid diacylglyceryl--trimethylhomoserine (DGTS). Over-expression of increased LD abundance and boosted TAG content. Purified recombinant ABHD1 hydrolyzed lyso-DGTS, producing a free fatty acid and a glyceryltrimethylhomoserine. droplet-embedded vesicles showed that ABHD1 promoted LD emergence. Taken together, these results identify ABHD1 as a new player in LD formation by its lipase activity on lyso-DGTS and by its distinct biophysical property. This study further suggests that lipases targeted to LDs and able to act on their polar lipid coat may be interesting tools to promote LD assembly in eukaryotic cells.

References

Bai F, Yu L, Shi J, Li-Beisson Y, Liu J . Long-chain acyl-CoA synthetases activate fatty acids for lipid synthesis, remodeling and energy production in Chlamydomonas. New Phytol. 2021; 233(2):823-837. DOI: 10.1111/nph.17813. View

Gu X, Cao L, Wu X, Li Y, Hu Q, Han D . A Lipid Bodies-Associated Galactosyl Hydrolase Is Involved in Triacylglycerol Biosynthesis and Galactolipid Turnover in the Unicellular Green Alga . Plants (Basel). 2021; 10(4). PMC: 8065580. DOI: 10.3390/plants10040675. View

Lord C, Thomas G, Brown J . Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism. Biochim Biophys Acta. 2013; 1831(4):792-802. PMC: 4765316. DOI: 10.1016/j.bbalip.2013.01.002. View

Li X, Moellering E, Liu B, Johnny C, Fedewa M, Sears B . A galactoglycerolipid lipase is required for triacylglycerol accumulation and survival following nitrogen deprivation in Chlamydomonas reinhardtii. Plant Cell. 2012; 24(11):4670-86. PMC: 3531859. DOI: 10.1105/tpc.112.105106. View

Chorlay A, Foret L, Thiam A . Origin of gradients in lipid density and surface tension between connected lipid droplet and bilayer. Biophys J. 2021; 120(24):5491-5503. PMC: 8715250. DOI: 10.1016/j.bpj.2021.11.022. View

Xu N, Zhang S, Cole R, McKinney S, Guo F, Haas J . The FATP1-DGAT2 complex facilitates lipid droplet expansion at the ER-lipid droplet interface. J Cell Biol. 2012; 198(5):895-911. PMC: 3432760. DOI: 10.1083/jcb.201201139. View

Kajikawa M, Sawaragi Y, Shinkawa H, Yamano T, Ando A, Kato M . Algal dual-specificity tyrosine phosphorylation-regulated kinase, triacylglycerol accumulation regulator1, regulates accumulation of triacylglycerol in nitrogen or sulfur deficiency. Plant Physiol. 2015; 168(2):752-64. PMC: 4453788. DOI: 10.1104/pp.15.00319. View

Moellering E, Benning C . RNA interference silencing of a major lipid droplet protein affects lipid droplet size in Chlamydomonas reinhardtii. Eukaryot Cell. 2009; 9(1):97-106. PMC: 2805299. DOI: 10.1128/EC.00203-09. View

Jang S, Kong F, Lee J, Choi B, Wang P, Gao P . CrABCA2 Facilitates Triacylglycerol Accumulation in under Nitrogen Starvation. Mol Cells. 2020; 43(1):48-57. PMC: 6999713. DOI: 10.14348/molcells.2019.0262. View

10.

Murakami H, Nobusawa T, Hori K, Shimojima M, Ohta H . Betaine Lipid Is Crucial for Adapting to Low Temperature and Phosphate Deficiency in . Plant Physiol. 2018; 177(1):181-193. PMC: 5933114. DOI: 10.1104/pp.17.01573. View

11.

Wang X, Wei H, Mao X, Liu J . Proteomics Analysis of Lipid Droplets from the Oleaginous Alga Chromochloris zofingiensis Reveals Novel Proteins for Lipid Metabolism. Genomics Proteomics Bioinformatics. 2019; 17(3):260-272. PMC: 6818385. DOI: 10.1016/j.gpb.2019.01.003. View

12.

Young D, Shachar-Hill Y . Large fluxes of fatty acids from membranes to triacylglycerol and back during N-deprivation and recovery in Chlamydomonas. Plant Physiol. 2021; 185(3):796-814. PMC: 8133548. DOI: 10.1093/plphys/kiaa071. View

13.

Yamaoka Y, Shin S, Choi B, Kim H, Jang S, Kajikawa M . The bZIP1 Transcription Factor Regulates Lipid Remodeling and Contributes to ER Stress Management in . Plant Cell. 2019; 31(5):1127-1140. PMC: 6533020. DOI: 10.1105/tpc.18.00723. View

14.

Chung J, Wu X, Lambert T, Lai Z, Walther T, Farese Jr R . LDAF1 and Seipin Form a Lipid Droplet Assembly Complex. Dev Cell. 2019; 51(5):551-563.e7. PMC: 7235935. DOI: 10.1016/j.devcel.2019.10.006. View

15.

Riekhof W, Sears B, Benning C . Annotation of genes involved in glycerolipid biosynthesis in Chlamydomonas reinhardtii: discovery of the betaine lipid synthase BTA1Cr. Eukaryot Cell. 2005; 4(2):242-52. PMC: 549322. DOI: 10.1128/EC.4.2.242-252.2005. View

16.

Chorlay A, Santinho A, Thiam A . Making Droplet-Embedded Vesicles to Model Cellular Lipid Droplets. STAR Protoc. 2020; 1(3):100116. PMC: 7757013. DOI: 10.1016/j.xpro.2020.100116. View

17.

Merchant S, Kropat J, Liu B, Shaw J, Warakanont J . TAG, you're it! Chlamydomonas as a reference organism for understanding algal triacylglycerol accumulation. Curr Opin Biotechnol. 2012; 23(3):352-63. DOI: 10.1016/j.copbio.2011.12.001. View

18.

Chorlay A, Monticelli L, Ferreira J, Ben Mbarek K, Ajjaji D, Wang S . Membrane Asymmetry Imposes Directionality on Lipid Droplet Emergence from the ER. Dev Cell. 2019; 50(1):25-42.e7. DOI: 10.1016/j.devcel.2019.05.003. View

19.

Thiam A, Farese Jr R, Walther T . The biophysics and cell biology of lipid droplets. Nat Rev Mol Cell Biol. 2013; 14(12):775-86. PMC: 4526153. DOI: 10.1038/nrm3699. View

20.

Farese Jr R, Walther T . Lipid droplets finally get a little R-E-S-P-E-C-T. Cell. 2009; 139(5):855-60. PMC: 3097139. DOI: 10.1016/j.cell.2009.11.005. View