ER-localized Phosphatidylethanolamine Synthase Plays a Conserved Role in Lipid Droplet Formation

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2021 Nov 24

PMID 34818062

Citations 8

Authors

Mehmet Oguz Gok

Natalie Ortiz Speer

W Mike Henne

Jonathan R Friedman

Affiliations

Soon will be listed here.

Abstract

The asymmetric distribution of phospholipids in membranes is a fundamental principle of cellular compartmentalization and organization. Phosphatidylethanolamine (PE), a nonbilayer phospholipid that contributes to organelle shape and function, is synthesized at several subcellular localizations via semiredundant pathways. Previously, we demonstrated in budding yeast that the PE synthase Psd1, which primarily operates on the mitochondrial inner membrane, is additionally targeted to the ER. While ER-localized Psd1 is required to support cellular growth in the absence of redundant pathways, its physiological function is unclear. We now demonstrate that ER-localized Psd1 sublocalizes on the ER to lipid droplet (LD) attachment sites and show it is specifically required for normal LD formation. We also find that the role of phosphatidylserine decarboxylase (PSD) enzymes in LD formation is conserved in other organisms. Thus we have identified PSD enzymes as novel regulators of LDs and demonstrate that both mitochondria and LDs in yeast are organized and shaped by the spatial positioning of a single PE synthesis enzyme.

Citing Articles

Effects of surfactin stress on gene expression and pathological changes in Spodoptera litura.

Zhang F, Liu Q, Wang Y, Yin J, Meng X, Wang J Sci Rep. 2024; 14(1):30357.

PMID: 39638883 PMC: 11621121. DOI: 10.1038/s41598-024-81946-2.

Membrane protein Bcsdr2 mediates biofilm integrity, hyphal growth and virulence of Botrytis cinerea.

Zhang W, Cao Y, Li H, Rasmey A, Zhang K, Shi L Appl Microbiol Biotechnol. 2024; 108(1):398.

PMID: 38940906 PMC: 11213811. DOI: 10.1007/s00253-024-13238-8.

A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Kumar A, Gok M, Nguyen K, Connor O, Reese M, Wideman J Curr Biol. 2024; 34(12):2606-2622.e9.

PMID: 38692277 PMC: 11187654. DOI: 10.1016/j.cub.2024.04.028.

Chemical inhibition of phosphatidylcholine biogenesis reveals its role in mitochondrial division.

Shiino H, Tashiro S, Hashimoto M, Sakata Y, Hosoya T, Endo T iScience. 2024; 27(3):109189.

PMID: 38420588 PMC: 10901091. DOI: 10.1016/j.isci.2024.109189.

A DRP-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Kumar A, Gok M, Nguyen K, Reese M, Wideman J, Munoz-Gomez S bioRxiv. 2023; .

PMID: 37873150 PMC: 10592917. DOI: 10.1101/2023.10.03.560745.

References

Gulshan K, Shahi P, Moye-Rowley W . Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance. Mol Biol Cell. 2009; 21(3):443-55. PMC: 2814789. DOI: 10.1091/mbc.e09-06-0519. View

Ruggiano A, Mora G, Buxo L, Carvalho P . Spatial control of lipid droplet proteins by the ERAD ubiquitin ligase Doa10. EMBO J. 2016; 35(15):1644-55. PMC: 4969576. DOI: 10.15252/embj.201593106. View

Wright R . Transmission electron microscopy of yeast. Microsc Res Tech. 2001; 51(6):496-510. DOI: 10.1002/1097-0029(20001215)51:6<496::AID-JEMT2>3.0.CO;2-9. View

Steenbergen R, Nanowski T, Beigneux A, Kulinski A, Young S, Vance J . Disruption of the phosphatidylserine decarboxylase gene in mice causes embryonic lethality and mitochondrial defects. J Biol Chem. 2005; 280(48):40032-40. PMC: 2888304. DOI: 10.1074/jbc.M506510200. View

Wood N, Kositangool P, Hariri H, Marchand A, Henne W . Nutrient Signaling, Stress Response, and Inter-organelle Communication Are Non-canonical Determinants of Cell Fate. Cell Rep. 2020; 33(9):108446. PMC: 9744185. DOI: 10.1016/j.celrep.2020.108446. View

Chan E, McQuibban G . Phosphatidylserine decarboxylase 1 (Psd1) promotes mitochondrial fusion by regulating the biophysical properties of the mitochondrial membrane and alternative topogenesis of mitochondrial genome maintenance protein 1 (Mgm1). J Biol Chem. 2012; 287(48):40131-9. PMC: 3504727. DOI: 10.1074/jbc.M112.399428. View

Sheff M, Thorn K . Optimized cassettes for fluorescent protein tagging in Saccharomyces cerevisiae. Yeast. 2004; 21(8):661-70. DOI: 10.1002/yea.1130. View

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

Kumar S, Chitraju C, Farese Jr R, Walther T, Burd C . Conditional targeting of phosphatidylserine decarboxylase to lipid droplets. Biol Open. 2021; 10(3). PMC: 7938800. DOI: 10.1242/bio.058516. View

10.

Friedman J, Mourier A, Yamada J, McCaffery J, Nunnari J . MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture. Elife. 2015; 4. PMC: 4434539. DOI: 10.7554/eLife.07739. View

11.

Birner R, Burgermeister M, SCHNEITER R, Daum G . Roles of phosphatidylethanolamine and of its several biosynthetic pathways in Saccharomyces cerevisiae. Mol Biol Cell. 2001; 12(4):997-1007. PMC: 32282. DOI: 10.1091/mbc.12.4.997. View

12.

Choudhary V, Golani G, Joshi A, Cottier S, Schneiter R, Prinz W . Architecture of Lipid Droplets in Endoplasmic Reticulum Is Determined by Phospholipid Intrinsic Curvature. Curr Biol. 2018; 28(6):915-926.e9. PMC: 5889118. DOI: 10.1016/j.cub.2018.02.020. View

13.

Friedman J, Kannan M, Toulmay A, Jan C, Weissman J, Prinz W . Lipid Homeostasis Is Maintained by Dual Targeting of the Mitochondrial PE Biosynthesis Enzyme to the ER. Dev Cell. 2018; 44(2):261-270.e6. PMC: 5975648. DOI: 10.1016/j.devcel.2017.11.023. View

14.

Longtine M, McKenzie 3rd A, DeMarini D, Shah N, Wach A, Brachat A . Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998; 14(10):953-61. DOI: 10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U. View

15.

Choudhary V, El Atab O, Mizzon G, Prinz W, Schneiter R . Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis. J Cell Biol. 2020; 219(7). PMC: 7337503. DOI: 10.1083/jcb.201910177. View

16.

Kuroda T, Tani M, Moriguchi A, Tokunaga S, Higuchi T, Kitada S . FMP30 is required for the maintenance of a normal cardiolipin level and mitochondrial morphology in the absence of mitochondrial phosphatidylethanolamine synthesis. Mol Microbiol. 2011; 80(1):248-65. DOI: 10.1111/j.1365-2958.2011.07569.x. View

17.

Fukasawa Y, Tsuji J, Fu S, Tomii K, Horton P, Imai K . MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites. Mol Cell Proteomics. 2015; 14(4):1113-26. PMC: 4390256. DOI: 10.1074/mcp.M114.043083. View

18.

Cartwright B, Binns D, Hilton C, Han S, Gao Q, Goodman J . Seipin performs dissectible functions in promoting lipid droplet biogenesis and regulating droplet morphology. Mol Biol Cell. 2014; 26(4):726-39. PMC: 4325842. DOI: 10.1091/mbc.E14-08-1303. View

19.

Ben Mbarek K, Ajjaji D, Chorlay A, Vanni S, Foret L, Thiam A . ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation. Dev Cell. 2017; 41(6):591-604.e7. DOI: 10.1016/j.devcel.2017.05.012. View

20.

Adeyo O, Horn P, Lee S, Binns D, Chandrahas A, Chapman K . The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets. J Cell Biol. 2011; 192(6):1043-55. PMC: 3063132. DOI: 10.1083/jcb.201010111. View