One of the best characterized fungal membrane microdomains is the MCC/eisosome. The MCC (membrane compartment of Can1) is an evolutionarily conserved ergosterol-rich plasma membrane domain. It is stabilized on its cytosolic face by the eisosome, a hemitubular protein complex composed of Bin/Amphiphysin/Rvs (BAR) domain-containing Pil1 and Lsp1. These two proteins bind directly to phosphatidylinositol 4,5-bisphosphate and promote the typical furrow-like shape of the microdomain, with highly curved edges and bottom. While some proteins display stable localization in the MCC/eisosome, others enter or leave it under particular conditions, such as misbalance in membrane lipid composition, changes in membrane tension, or availability of specific nutrients. These findings reveal that the MCC/eisosome, a plasma membrane microdomain with distinct morphology and lipid composition, acts as a multifaceted regulator of various cellular processes including metabolic pathways, cellular morphogenesis, signalling cascades, and mRNA decay. In this minireview, we focus on the MCC/eisosome's proposed role in the regulation of lipid metabolism. While the molecular mechanisms of the MCC/eisosome function are not completely understood, the idea of intracellular processes being regulated at the plasma membrane, the foremost barrier exposed to environmental challenges, is truly exciting.

Department of Microscopy Institute of Experimental Medicine Academy of Sciences of the Czech Republic 14220 Prague Czech Republic

Zobrazit více v PubMed

Malinska K., Malinsky J., Opekarova M., Tanner W. Visualization of protein compartmentation within the plasma membrane of living yeast cellls. Mol. Biol. Cell. 2003;14:4427–4436. doi: 10.1091/mbc.e03-04-0221. PubMed DOI PMC

Malinska K., Malinsky J., Opekarova M., Tanner W. Distribution of Can1p into stable domains reflects lateral protein segregation within the plasma membrane of living S. cerevisiae cells. J. Cell Sci. 2004;117:6031–6041. doi: 10.1242/jcs.01493. PubMed DOI

Grossmann G., Opekarová M., Malinsky J., Weig-Meckl I., Tanner W. Membrane potential governs lateral segregation of plasma membrane proteins and lipids in yeast. EMBO J. 2007;26:1–8. doi: 10.1038/sj.emboj.7601466. PubMed DOI PMC

Bianchi F., Syga L., Moiset G., Spakman D., Schavemaker P.E., Punter C.M., Seinen A.B., Van Oijen A.M., Robinson A., Poolman B. Steric exclusion and protein conformation determine the localization of plasma membrane transporters. Nat. Commun. 2018;9 doi: 10.1038/s41467-018-02864-2. PubMed DOI PMC

Busto J.V., Elting A., Haase D., Spira F., Kuhlman J., Schäfer-Herte M., Wedlich-Söldner R. Lateral plasma membrane compartmentalization links protein function and turnover. EMBO J. 2018;37:1–17. doi: 10.15252/embj.201899473. PubMed DOI PMC

Grossmann G., Malinsky J., Stahlschmidt W., Loibl M., Weig-Meckl I., Frommer W.B., Opekarová M., Tanner W. Plasma membrane microdomains regulate turnover of transport proteins in yeast. J. Cell Biol. 2008;183:1075–1088. doi: 10.1083/jcb.200806035. PubMed DOI PMC

Fröhlich F., Moreira K., Aguilar P.S., Hubner N.C., Mann M., Walter P., Walther T.C. A genome-wide screen for genes affecting eisosomes reveals Nce102 function in sphingolipid signaling. J. Cell Biol. 2009;185:1227–1242. doi: 10.1083/jcb.200811081. PubMed DOI PMC

Walther T.C., Brickner J.H., Aguilar P.S., Bernales S., Pantoja C., Walter P. Eisosomes mark static sites of endocytosis. Nature. 2006;439:998–1003. doi: 10.1038/nature04472. PubMed DOI

Stradalova V., Stahlschmidt W., Grossmann G., Blazikova M., Rachel R., Tanner W., Malinsky J. Furrow-like invaginations of the yeast plasma membrane correspond to membrane compartment of Can1. J. Cell Sci. 2009;122:2887–2894. doi: 10.1242/jcs.051227. PubMed DOI

Zhang X., Lester R.L., Dickson R.C. Pil1p and Lsp1p negatively regulate the 3-phosphoinositide-dependent protein kinase-like kinase Pkh1p and downstream signaling pathways Pkc1p and Ypk1p. J. Biol. Chem. 2004;279:22030–22038. doi: 10.1074/jbc.M400299200. PubMed DOI

Olivera-Couto A., Grana M., Harispe L., Aguilar P.S. The eisosome core is composed of BAR domain proteins. Mol. Biol. Cell. 2011;22:2360–2372. doi: 10.1091/mbc.e10-12-1021. PubMed DOI PMC

Kabeche R., Baldissard S., Hammond J., Howard L., Moseley J.B. The filament-forming protein Pil1 assembles linear eisosomes in fission yeast. Mol. Biol. Cell. 2011;22:4059–4067. doi: 10.1091/mbc.e11-07-0605. PubMed DOI PMC

Karotki L., Huiskonen J.T., Stefan C.J., Ziółkowska N.E., Roth R., Surma M.A., Krogan N.J., Emr S.D., Heuser J., Grünewald K., et al. Eisosome proteins assemble into a membrane scaffold. J. Cell Biol. 2011;195:889–902. doi: 10.1083/jcb.201104040. PubMed DOI PMC

Kabeche R., Roguev A., Krogan N.J., Moseley J.B. A Pil1-Sle1-Syj1-Tax4 functional pathway links eisosomes with PI(4,5)P2 regulation. J. Cell Sci. 2014;127:1318–1326. doi: 10.1242/jcs.143545. PubMed DOI PMC

Lee J.-H., Heuser J.E., Roth R., Goodenough U. Eisosome Ultrastructure and Evolution in Fungi, Microalgae, and Lichens. Eukaryot. Cell. 2015;14:1017–1042. doi: 10.1128/EC.00106-15. PubMed DOI PMC

Blyth J., Makrantoni V., Baton R.E., Spanos C., Rappsilber J., Marston A.L. Genes Important for Schizosaccharomyces pombe Genomics Screen. Genetics. 2018;208:589–603. doi: 10.1534/genetics.117.300527. PubMed DOI PMC

Wang H.X., Douglas L.M., Veselá P., Rachel R., Malinsky J., Konopka J.B. Eisosomes promote the ability of Sur7 to regulate plasma membrane organization in Candida albicans. Mol. Biol. Cell. 2016;27:1663–1675. doi: 10.1091/mbc.E16-01-0065. PubMed DOI PMC

Douglas L.M., Wang H.X., Keppler-Ross S., Dean N., Konopka J.B. Sur7 Promotes Plasma Membrane Organization and Is Needed for Resistance to Stressful Conditions and to the Invasive Growth and Virulence of Candida albicans. mBio. 2012;3:1–12. doi: 10.1128/mBio.00254-11. PubMed DOI PMC

Douglas L.M., Konopka J.B. Plasma membrane architecture protects Candida albicans from killing by copper. PLoS Genet. 2019;15:1–26. doi: 10.1371/journal.pgen.1007911. PubMed DOI PMC

Carman G.M., Henry S.A. Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes. Prog. Lipid Res. 1999;38:361–399. doi: 10.1016/S0163-7827(99)00010-7. PubMed DOI

Frohlich F., Christiano R., Olson D.K., Alcazar-Roman A., DeCamilli P., Walther T.C. A role for eisosomes in maintenance of plasma membrane phosphoinositide levels. Mol. Biol. Cell. 2014;25:2797–2806. doi: 10.1091/mbc.e13-11-0639. PubMed DOI PMC

Berchtold D., Piccolis M., Chiaruttini N., Riezman I., Riezman H., Roux A., Walther T.C., Loewith R. Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis. Nat. Cell Biol. 2012;14:542–547. doi: 10.1038/ncb2480. PubMed DOI

Grousl T., Opekarová M., Stradalova V., Hasek J., Malinsky J. Evolutionarily conserved 5′-3′ exoribonuclease Xrn1 accumulates at plasma membrane-associated eisosomes in post-diauxic yeast. PLoS ONE. 2015;10:1–19. doi: 10.1371/journal.pone.0122770. PubMed DOI PMC

Pedroso N., Matias A.C., Cyrne L., Antunes F., Borges C., Malhó R., de Almeida R.F.M., Herrero E., Marinho H.S. Modulation of plasma membrane lipid profile and microdomains by H2O2 in Saccharomyces cerevisiae. Free Radic. Biol. Med. 2009;46:289–298. doi: 10.1016/j.freeradbiomed.2008.10.039. PubMed DOI

Dupont S., Beney L., Ritt J.F., Lherminier J., Gervais P. Lateral reorganization of plasma membrane is involved in the yeast resistance to severe dehydration. Biochimica et Biophysica Acta Biomembranes. 2010;1798:975–985. doi: 10.1016/j.bbamem.2010.01.015. PubMed DOI

Needham D., Nunn R.S. Elastic deformation and failure of lipid bilayer membranes containing cholesterol. Biophys. J. 1990;58:997–1009. doi: 10.1016/S0006-3495(90)82444-9. PubMed DOI PMC

Bretscher M.S., Munro S. Cholesterol and the Golgi apparatus. Science. 1993;261:1280–1281. doi: 10.1126/science.8362242. PubMed DOI

Simons K., Ikonen E. Functional rafts in cell membranes. Nature. 1997;387:569–572. doi: 10.1038/42408. PubMed DOI

Zinser E., Paltauf F., Daum G. Sterol composition of yeast organelle membranes and subcellular distribution of enzymes involved in sterol metabolism. J. Bacteriol. 1993;175:2853–2858. doi: 10.1128/jb.175.10.2853-2858.1993. PubMed DOI PMC

Munn A.L., Heese-Peck A., Stevenson B.J., Pichler H., Riezman H. Specific Sterols Required for the Internalization Step of Endocytosis in Yeast. Mol. Biol. Cell. 1999;10:3943–3957. doi: 10.1091/mbc.10.11.3943. PubMed DOI PMC

Heese-Peck A., Pichler H., Zanolari B., Watanabe R., Daum G., Riezman H. Multiple functions of sterols in yeast endocytosis. Mol. Biol. Cell. 2002;13:2664–2680. doi: 10.1091/mbc.e02-04-0186. PubMed DOI PMC

Schneiter R., Brügger B., Sandhoff R., Zellnig G., Leber A., Lampl M., Athenstaedt K., Hrastnik C., Eder S., Daum G., et al. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane. J. Cell Biol. 1999;146:741–754. doi: 10.1083/jcb.146.4.741. PubMed DOI PMC

Munro S. Lipid rafts: Elusive or illusive? Cell. 2003;115:377–388. doi: 10.1016/S0092-8674(03)00882-1. PubMed DOI

Solanko L.M., Sullivan D.P., Sere Y.Y., Szomek M., Lunding A., Solanko K.A., Pizovic A., Stanchev L.D., Pomorski T.G., Menon A.K., et al. Ergosterol is mainly located in the cytoplasmic leaflet of the yeast plasma membrane. Traffic. 2018;19:198–214. doi: 10.1111/tra.12545. PubMed DOI

Van Meer G., Voelker D.R., Feigenson G.W. Membrane lipids: Where they are and how they behave. Nat. Rev. Mol. Cell Biol. 2008;9:112–124. doi: 10.1038/nrm2330. PubMed DOI PMC

Bagnat M., Simons K. Cell surface polarization during yeast mating. Proc. Natl. Acad. Sci. USA. 2002;99:14183–14188. doi: 10.1073/pnas.172517799. PubMed DOI PMC

Wachtler V. Sterol-rich plasma membrane domains in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 2003;116:867–874. doi: 10.1242/jcs.00299. PubMed DOI

Nichols C.B., Fraser J.A., Heitman J. PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Mol. Biol. Cell. 2004;15:4476–4489. doi: 10.1091/mbc.e04-05-0370. PubMed DOI PMC

Grossmann G., Opekarova M., Novakova L., Stolz J., Tanner W. Lipid Raft-Based Membrane Compartmentation of a Plant Transport Protein Expressed in Saccharomyces cerevisiae. Eukaryot. Cell. 2006;5:945–953. doi: 10.1128/EC.00206-05. PubMed DOI PMC

Proszynski T.J., Klemm R., Bagnat M., Gaus K., Simons K. Plasma membrane polarization during mating in yeast cells. J. Cell Biol. 2006;173:861–866. doi: 10.1083/jcb.200602007. PubMed DOI PMC

Martin S.W., Konopka J.B. Lipid raft polarization contributes to hyphal growth in Candida albicans. Eukaryot. Cell. 2004;3:675–684. doi: 10.1128/EC.3.3.675-684.2004. PubMed DOI PMC

Pearson C.L., Xu K., Sharpless K.E., Harris S.D. MesA, a novel fungal protein required for the stabilization of polarity axes in Aspergillus nidulans. Mol. Biol. Cell. 2004;15:3658–3672. doi: 10.1091/mbc.e03-11-0803. PubMed DOI PMC

Malinsky J., Opekarová M., Grossmann G., Tanner W. Membrane Microdomains, Rafts, and Detergent-Resistant Membranes in Plants and Fungi. Annu. Rev. Plant Biol. 2013;64:501–529. doi: 10.1146/annurev-arplant-050312-120103. PubMed DOI

Toulmay A., Prinz W.A. Direct imaging reveals stable, micrometer-scale lipid domains that segregate proteins in live cells. J. Cell Biol. 2013;202:35–44. doi: 10.1083/jcb.201301039. PubMed DOI PMC

Tsuji T., Fujimoto M., Tatematsu T., Cheng J., Orii M., Takatori S., Fujimoto T. Niemann-Pick type C proteins promote microautophagy by expanding raft-like membrane domains in the yeast vacuole. eLife. 2017;6:1–34. doi: 10.7554/eLife.25960. PubMed DOI PMC

Zinser E., Daum G. Isolation and biochemical characterization of organelles from the yeast, Saccharomyces cerevisiae. Yeast. 1995;11:493–536. doi: 10.1002/yea.320110602. PubMed DOI

Lange Y., Steck T.L. The role of intracellular cholesterol transport in cholesterol homeostasis. Trends Cell Biol. 1996;6:205–208. doi: 10.1016/0962-8924(96)20016-9. PubMed DOI

Wang C.W., Miao Y.H., Chang Y.S. A sterol-enriched vacuolar microdomain mediates stationary phase lipophagy in budding yeast. J. Cell Biol. 2014;206:357–366. doi: 10.1083/jcb.201404115. PubMed DOI PMC

Dupre S., Haguenauer-Tsapis R. Raft partitioning of the yeast uracil permease during trafficking along the endocytic pathway. Traffic. 2003;4:83–96. doi: 10.1034/j.1600-0854.2003.40204.x. PubMed DOI

Umebayashi K., Nakano A. Ergosterol is required for targeting of tryptophan permease to the yeast plasma membrane. J. Cell Biol. 2003;161:1117–1131. doi: 10.1083/jcb.200303088. PubMed DOI PMC

Douglas L.M., Wang H.X., Konopka J.B. The MARVEL Domain Protein Nce102 Regulates Actin Organization and Invasive Growth of Candida albicans. mBio. 2013;4:1–12. doi: 10.1128/mBio.00723-13. PubMed DOI PMC

Athanasopoulos A., Gournas C., Amillis S., Sophianopoulou V. Characterization of AnNce102 and its role in eisosome stability and sphingolipid biosynthesis. Sci. Rep. 2015;5:1–16. doi: 10.1038/srep15200. PubMed DOI PMC

Loibl M., Grossmann G., Stradalova V., Klingl A., Rachel R., Tanner W., Malinsky J., Opekarová M. C terminus of Nce 102 determines the structure and function of microdomains in the Saccharomyces cerevisiae plasma membrane. Eukaryot. Cell. 2010;9:1184–1192. doi: 10.1128/EC.00006-10. PubMed DOI PMC

Agarwal A.K., Rogers P.D., Baerson S.R., Jacob M.R., Barker K.S., Cleary J.D., Walker L.A., Nagle D.G., Clark A.M. Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae. J. Biol. Chem. 2003;278:34998–35015. doi: 10.1074/jbc.M306291200. PubMed DOI

Wilcox L.J., Balderes D.A., Wharton B., Tinkelenberg A.H., Rao G., Sturley S.L. Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast. J. Biol. Chem. 2002;277:32466–32472. doi: 10.1074/jbc.M204707200. PubMed DOI

Vik A., Rine J. Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 2001;21:6395–6405. doi: 10.1128/MCB.21.19.6395-6405.2001. PubMed DOI PMC

Yang H., Tong J., Lee C.W., Ha S., Eom S.H., Im Y.J. Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2. Nat. Commun. 2015;6:1–13. doi: 10.1038/ncomms7129. PubMed DOI

Woods K., Höfken T. The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. Mol. Microbiol. 2016;99:512–527. doi: 10.1111/mmi.13244. PubMed DOI

Foster H.A., Cui M., Naveenathayalan A., Unden H., Schwanbeck R., Höfken T. The zinc cluster protein Sut1 contributes to filamentation in Saccharomyces cerevisiae. Eukaryot. Cell. 2013;12:244–253. doi: 10.1128/EC.00214-12. PubMed DOI PMC

Blanda C., Höfken T. Regulation of mating in the budding yeast Saccharomyces cerevisiae by the zinc cluster proteins Sut1 and Sut2. Biochem. Biophys. Res. Commun. 2013;438:66–70. doi: 10.1016/j.bbrc.2013.07.027. PubMed DOI

Shively C.A., Eckwahl M.J., Dobry C.J., Mellacheruvu D., Nesvizhskii A., Kumar A. Genetic Networks Inducing Invasive Growth in Saccharomyces cerevisiae Identified Through Systematic Genome-Wide Overexpression. Genetics. 2013;193:1297–1310. doi: 10.1534/genetics.112.147876. PubMed DOI PMC

Kubler E., Dohlman H.G., Lisanti M.P. Identification of triton X-100 insoluble membrane domains in the yeast Saccharomyces cerevisiae—Lipid requirements for targeting of heterotrimeric G-protein subunits. J. Biol. Chem. 1996;271:32975–32980. doi: 10.1074/jbc.271.51.32975. PubMed DOI

Bagnat M., Keranen S., Shevchenko A., Simons K. Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast. Proc. Natl. Acad. Sci. USA. 2000;97:3254–3259. doi: 10.1073/pnas.97.7.3254. PubMed DOI PMC

Souza C.M., Pichler H. Lipid requirements for endocytosis in yeast. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2007;1771:442–454. doi: 10.1016/j.bbalip.2006.08.006. PubMed DOI

Patton J.L., Lester R.L. The phosphoinositol sphingolipids of Saccharomyces cerevisiae are highly localized in the plasma membrane. J. Bacteriol. 1991;173:3101–3108. doi: 10.1128/jb.173.10.3101-3108.1991. PubMed DOI PMC

Lester R.L., Wells G.B., Oxford G., Dickson R.C. Mutant strains of Saccharomyces cerevisiae lacking sphingolipids synthesize novel inositol glycerophospholipids that mimic sphingolipid structures. J. Biol. Chem. 1993;268:845–856. PubMed

Lee M.C.S., Hamamoto S., Schekman R. Ceramide Biosynthesis Is Required for the Formation of the Oligomeric H+-ATPase Pma1p in the Yeast Endoplasmic Reticulum. J. Biol. Chem. 2002;277:22395–22401. doi: 10.1074/jbc.M200450200. PubMed DOI

Wang Q., Chang A. Sphingoid base synthesis is required for oligomerization and cell surface stability of the yeast plasma membrane ATPase, Pma1. Proc. Natl. Acad. Sci. USA. 2002;99:12853–12858. doi: 10.1073/pnas.202115499. PubMed DOI PMC

Lauwers E., Grossmann G., André B. Evidence for coupled biogenesis of yeast Gap1 permease and sphingolipids: Essential role in transport activity and normal control by ubiquitination. Mol. Biol. Cell. 2007;18:3068–3080. doi: 10.1091/mbc.e07-03-0196. PubMed DOI PMC

Serrano R., Kielland-Brandt M.C., Fink G.R. Yeast plasma membrane ATPase is essential for growth and has homology with (Na+ + K+), K+- and Ca2+-ATPases. Nature. 1986;319:689–693. doi: 10.1038/319689a0. PubMed DOI

Serrano R. Structure and function of proton translocafing ATPase in plasma membranes of plants and fungi. Biochem. Biophys. Acta. 1988;947:1–28. PubMed

Stanbrough M., Magasanik B. Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae. J. Bacterial. 1995;177:94–102. doi: 10.1128/jb.177.1.94-102.1995. PubMed DOI PMC

Chung N., Jenkins G., Hannun Y.A., Heitman J., Obeid L.M. Sphingolipids signal heat stress-induced ubiquitin-dependent proteolysis. J. Biol. Chem. 2000;275:17229–17232. doi: 10.1074/jbc.C000229200. PubMed DOI

Cowart L.A., Okamoto Y., Pinto F.R., Gandy J.L., Almeida J.S., Hannun Y.A. Roles for sphingolipid biosynthesis in mediation of specific programs of the heat stress response determined through gene expression profiling. J. Biol. Chem. 2003;278:30328–30338. doi: 10.1074/jbc.M300656200. PubMed DOI

Dickson R.C., Nagiec E.E., Skrzypek M., Tillman P., Wells G.B., Lester R.L. Sphingolipids are potential heat stress signals in Saccharomyces. J. Biol. Chem. 1997;272:30196–30200. doi: 10.1074/jbc.272.48.30196. PubMed DOI

Jenkins G.M. The emerging role for sphingolipids in the eukaryotic heat shock response. Cell. Mol. Life Sci. 2003;60:701–710. doi: 10.1007/s00018-003-2239-0. PubMed DOI PMC

Wells G.B., Dickson R.C., Lester R.L. Heat-induced Elevation of Ceramide in Saccharomyces cerevisiae via de Novo Synthesis. J. Biol. Chem. 1998;273:7235–7243. doi: 10.1074/jbc.273.13.7235. PubMed DOI

Levin D.E. Cell Wall Integrity Signaling in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 2005;69:262–291. doi: 10.1128/MMBR.69.2.262-291.2005. PubMed DOI PMC

Liu M., Huang C., Polu S.R., Schneiter R., Chang A. Regulation of sphingolipid synthesis through Orm1 and Orm2 in yeast. J. Cell Sci. 2012;125:2428–2435. doi: 10.1242/jcs.100578. PubMed DOI PMC

Piña F., Yagisawa F., Obara K., Gregerson J.D., Kihara A., Niwa M. Sphingolipids activate the endoplasmic reticulum stress surveillance pathway. J. Cell Biol. 2018;217:495–505. doi: 10.1083/jcb.201708068. PubMed DOI PMC

Friant S. Increased protein kinase or decreased PP2A activity bypasses sphingoid base requirement in endocytosis. EMBO J. 2000;19:2834–2844. doi: 10.1093/emboj/19.12.2834. PubMed DOI PMC

Zanolari B., Friant S., Funato K., Suetterlin C., Stevenson B.J., Riezman H. Sphingoid base synthesis requirement for endocytosis in Saccharomyces cerevisiae. EMBO J. 2000;19:2824–2833. doi: 10.1093/emboj/19.12.2824. PubMed DOI PMC

Dickson R.C. Roles for Sphingolipids in Saccharomyces cerevisiae. In: Chalfant C., DelPoeta M., editors. Sphingolipids as Signaling and Regulatory Molecules. Volume 688. Springer; Berlin, Germany: 2010. pp. 217–231. PubMed PMC

Frisz J.F., Lou K., Klitzing H.A., Hanafin W.P., Lizunov V., Wilson R.L., Carpenter K.J., Kim R., Hutcheon I.D., Zimmerberg J., et al. Direct chemical evidence for sphingolipid domains in the plasma membranes of fibroblasts. Proc. Natl. Acad. Sci. USA. 2013;110:E613–E622. doi: 10.1073/pnas.1216585110. PubMed DOI PMC

Frisz J.F., Klitzing H.A., Lous K., Hutcheon I.D., Weber P.K., Zimmerberg J., Kraft M.L. Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol. J. Biol. Chem. 2013;288:16855–16861. doi: 10.1074/jbc.M113.473207. PubMed DOI PMC

Aresta-Branco F., Cordeiro A.M., Marinho H.S., Cyrne L., Antunes F., de Almeida R.F.M. Gel Domains in the Plasma Membrane of Saccharomyces cerevisiae: Highly Ordered, Ergosterol-Free, And Sphingolipid-Enriched Lipid Rafts. J. Biol. Chem. 2011;286:5043–5054. doi: 10.1074/jbc.M110.154435. PubMed DOI PMC

Vecer J., Vesela P., Malinsky J., Herman P. Sphingolipid levels crucially modulate lateral microdomain organization of plasma membrane in living yeast. FEBS Lett. 2014;588:443–449. doi: 10.1016/j.febslet.2013.11.038. PubMed DOI

Herman P., Vecer J., Opekarova M., Vesela P., Jancikova I., Zahumensky J., Malinsky J. Depolarization affects the lateral microdomain structure of yeast plasma membrane. FEBS J. 2015;282:419–434. doi: 10.1111/febs.13156. PubMed DOI

Malinsky J., Tanner W., Opekarova M. Transmembrane voltage: Potential to induce lateral microdomains. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2016;1861:806–811. doi: 10.1016/j.bbalip.2016.02.012. PubMed DOI

Spira F., Mueller N.S., Beck G., Von Olshausen P., Beig J., Wedlich-Söldner R. Patchwork organization of the yeast plasma membrane into numerous coexisting domains. Nat. Cell Biol. 2012;14:640–648. doi: 10.1038/ncb2487. PubMed DOI

Breslow D.K., Collins S.R., Bodenmiller B., Aebersold R., Simons K., Shevchenko A., Ejsing C.S., Weissman J.S. Orm family proteins mediate sphingolipid homeostasis. Nature. 2010;463:1048–1053. doi: 10.1038/nature08787. PubMed DOI PMC

Han S., Lone M.A., Schneiter R., Chang A. Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control. Proc. Natl. Acad. Sci. USA. 2010;107:5851–5856. doi: 10.1073/pnas.0911617107. PubMed DOI PMC

Hjelmqvist L., Tuson M., Marfany G., Herrero E., Balcells S., Gonzalez-Duarte R. ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins. Genome Biol. 2002;3 doi: 10.1186/gb-2002-3-6-research0027. PubMed DOI PMC

Funato K., Vallee B., Riezman H. Biosynthesis and Trafficking of Sphingolipids in the Yeast Saccharomyces cerevisiae. Biochemistry. 2002;41:15105–15113. doi: 10.1021/bi026616d. PubMed DOI

Gable K., Han G., Monaghan E., Bacikova D., Natarajan M., Williams R., Dunn T.M. Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J. Biol. Chem. 2002;277:10194–10200. doi: 10.1074/jbc.M107873200. PubMed DOI

Han G., Gupta S.D., Gable K., Bacikova D., Sengupta N., Somashekarappa N., Proia R.L., Harmon J.M., Dunn T.M. The ORMs interact with transmembrane domain 1 of Lcb1 and regulate serine palmitoyltransferase oligomerization, activity and localization. Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids. 2019;1864:245–259. doi: 10.1016/j.bbalip.2018.11.007. PubMed DOI PMC

Casamayor A., Torrance P.D., Kobayashi T., Thorner J., Alessi D.R. Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr. Biol. 1999;9:S184–S186. doi: 10.1016/S0960-9822(99)80088-8. PubMed DOI

Roelants F.M., Breslow D.K., Muir A., Weissman J.S., Thorner J. Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA. 2011;108:19222–19227. doi: 10.1073/pnas.1116948108. PubMed DOI PMC

Gururaj C., Federman R., Chang A. Orm proteins integrate multiple signals to maintain sphingolipid homeostasis. J. Biol. Chem. 2013;288:20453–20463. doi: 10.1074/jbc.M113.472860. PubMed DOI PMC

Kimberlin A.N., Han G., Chen M., Cahoon R.E., Luttgeharm K.D., Stone J.M., Markham J.E., Dunn T.M., Cahoon E.B. ORM Expression Alters Sphingolipid Homeostasis and Differentially Affects Ceramide Synthase Activity. Plant Physiol. 2016;172:00965. doi: 10.1104/pp.16.00965. PubMed DOI PMC

Roelants F.M., Torrance P.D., Bezman N., Thorner J. Pkh1 and Pkh2 differentially phosphorylate and activate Ypk1 and Ykr2 and define protein kinase modules required for maintenance of cell wall integrity. Mol. Biol. Cell. 2002;13:3005–3028. doi: 10.1091/mbc.e02-04-0201. PubMed DOI PMC

Roelants F.M., Torrance P.D., Thorner J. Differential roles of PDK1- and PDK2- phosphorylation sites in the yeast AGC kinases Ypk1, Pkc1 and Sch9. Microbiology. 2004;150:3289–3304. doi: 10.1099/mic.0.27286-0. PubMed DOI

Kamada Y., Fujioka Y., Suzuki N.N., Inagaki F., Wullschleger S., Loewith R., Hall M.N., Ohsumi Y. Tor2 Directly Phosphorylates the AGC Kinase Ypk2 To Regulate Actin Polarization. Mol. Cell. Biol. 2005;25:7239–7248. doi: 10.1128/MCB.25.16.7239-7248.2005. PubMed DOI PMC

Sun Y., Miao Y., Yamane Y., Zhang C., Shokat K.M., Takematsu H., Kozutsumi Y., Drubin D.G. Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via the Pkh-Ypk and Cdc55-PP2A pathways. Mol. Biol. Cell. 2012;23:2388–2398. doi: 10.1091/mbc.e12-03-0209. PubMed DOI PMC

Leskoske K.L., Roelants F.M., Marshall M.N.M., Hill J.M., Thorner J. The stress-sensing TORC2 complex activates yeast AGC-family protein kinase ypk1 at multiple novel sites. Genetics. 2017;207:179–195. doi: 10.1534/genetics.117.1124. PubMed DOI PMC

Walther T.C., Aguilar P.S., Fröhlich F., Chu F., Moreira K., Burlingame A.L., Walter P. Pkh-kinases control eisosome assembly and organization. EMBO J. 2007;26:4946–4955. doi: 10.1038/sj.emboj.7601933. PubMed DOI PMC

Berchtold D., Walther T.C. TORC2 Plasma Membrane Localization Is Essential for Cell Viability and Restricted to a Distinct Domain. Mol. Biol. Cell. 2009;20:1565–1575. doi: 10.1091/mbc.e08-10-1001. PubMed DOI PMC

Luo G., Gruhler A., Liu Y., Jensen O.N., Dickson R.C. The sphingolipid long-chain base-Pkh1/2-Ypk1/2 signaling pathway regulates eisosome assembly and turnover. J. Biol. Chem. 2008;283:10433–10444. doi: 10.1074/jbc.M709972200. PubMed DOI PMC

Baxter B.K., DiDone L., Ogu D., Schor S., Krysan D.J. Identification, in Vitro Activity and Mode of Action of Phosphoinositide-Dependent-1 Kinase Inhibitors as Antifungal Molecules. ACS Chem. Biol. 2011;6:502–510. doi: 10.1021/cb100399x. PubMed DOI PMC

Audhya A., Loewith R., Parsons A.B., Gao L., Tabuchi M., Zhou H., Boone C., Hall M.N., Emr S.D. Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J. 2004;23:3747–3757. doi: 10.1038/sj.emboj.7600384. PubMed DOI PMC

Niles B.J., Mogri H., Hill A., Vlahakis A., Powers T. Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex 2 (TORC2) and its effector proteins Slm1 and Slm2. Proc. Natl. Acad. Sci. USA. 2012;109:1536–1541. doi: 10.1073/pnas.1117563109. PubMed DOI PMC

García-Marqués S., Randez-Gil F., Dupont S., Garre E., Prieto J.A. Sng1 associates with Nce102 to regulate the yeast Pkh–Ypk signalling module in response to sphingolipid status. BBA Mol. Cell Res. 2016;1863:1319–1333. doi: 10.1016/j.bbamcr.2016.03.025. PubMed DOI

García-López M.C., Mirón-García M.C., Garrido-Godino A.I., Mingorance C., Navarro F. Overexpression of SNG1 causes 6-azauracil resistance in Saccharomyces cerevisiae. Curr. Genet. 2010;56:251–263. doi: 10.1007/s00294-010-0297-z. PubMed DOI

Cabiscol E., Herrero E., Ros J. Oxidative stress promotes specific protein damage in Saccharomyces cerevisiae. Biochemistry. 2000;275:27393–27398. doi: 10.1074/jbc.M003140200. PubMed DOI

Breitenbach M., Laun P., Dickinson J.R., Klocker A., Rinnerthaler M., Dawes I.W., Aung-htut M.T., Breitenbach-koller L., Caballero A., Nyström T., et al. The Role of Mitochondria in the Aging Processes of Yeast. In: Breitenbach M., Jazwinski S.M., Laun P., editors. Aging Research in Yeast. Volume 57. Springer; New York, NY, USA: 2012. pp. 55–78. PubMed

Niles B.J., Joslin A.C., Fresques T., Powers T. TOR Complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and regulating ROS accumulation. Cell Rep. 2014;6:541–552. doi: 10.1016/j.celrep.2013.12.040. PubMed DOI PMC

Mulet J.M., Martin D.E., Loewith R., Hall M.N. Mutual antagonism of target of rapamycin and calcineurin signaling. J. Biol. Chem. 2006;281:33000–33007. doi: 10.1074/jbc.M604244200. PubMed DOI

Tabuchi M., Audhya A., Parsons A.B., Boone C., Emr S.D. The Phosphatidylinositol 4,5-Biphosphate and TORC2 Binding Proteins Slm1 and Slm2 Function in Sphingolipid Regulation. Mol. Cell. Biol. 2006;26:5861–5875. doi: 10.1128/MCB.02403-05. PubMed DOI PMC

Cyert M.S. Calcineurin signaling in Saccharomyces cerevisiae: How yeast go crazy in response to stress. Biochem. Biophys. Res. Commun. 2003;311:1143–1150. doi: 10.1016/S0006-291X(03)01552-3. PubMed DOI

Deutscher D., Meilijson I., Kupiec M., Ruppin E. Multiple knockout analysis of genetic robustness in the yeast metabolic network. Nat. Genet. 2006;38:993–998. doi: 10.1038/ng1856. PubMed DOI

Zahumensky J., Malinsky J. Intracellular engagement of Nce102-like proteins. Unpublished.

Jenkins G.M., Richards A., Wahl T., Mao C., Obeid L., Hannun Y. Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J. Biol. Chem. 1997;272:32566–32572. doi: 10.1074/jbc.272.51.32566. PubMed DOI

Skrzypek M.S., Nagiec M.M., Lester R.L., Dickson R.C. Analysis of phosphorylated sphingolipid long-chain bases reveals potential roles in heat stress and growth control in Saccharomyces. J. Bacteriol. 1999;181:1134–1140. PubMed PMC

Vaskovicova K., Awadova T., Vesela P., Balazova M., Opekarova M., Malinsky J. mRNA decay is regulated via sequestration of the conserved 5′-3′ exoribonuclease Xrn1 at eisosome in yeast. Eur. J. Cell Biol. 2017;96:591–599. doi: 10.1016/j.ejcb.2017.05.001. PubMed DOI

Gournas C., Gkionis S., Carquin M., Twyffels L., Tyteca D., André B. Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains. Proc. Natl. Acad. Sci. USA. 2018;115:E3145–E3154. doi: 10.1073/pnas.1719462115. PubMed DOI PMC

Payrastre B., Missy K., Giuriato S., Bodin S., Plantavid M., Gratacap M.P. Phosphoinositides: Key players in cell signalling, in time and space. Cell. Signal. 2001;13:377–387. doi: 10.1016/S0898-6568(01)00158-9. PubMed DOI

Balla T. Phosphoinositides: Tiny Lipids with Giant Impact on Cell Regulation. Physiol. Rev. 2013;93:1019–1137. doi: 10.1152/physrev.00028.2012. PubMed DOI PMC

Posor Y., Eichhorn-Grünig M., Haucke V. Phosphoinositides in endocytosis. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2015;1851:794–804. doi: 10.1016/j.bbalip.2014.09.014. PubMed DOI

Fruman D.A., Meyers R.E., Cantley L.C. Phosphoinositide kinases. Ann. Rev. Biochem. 1998;67:481–507. doi: 10.1146/annurev.biochem.67.1.481. PubMed DOI

Martin T.F.J. Phosphoinositide lipids as signaling molecules: Common themes for signal transduction, cytoskeletal regulation, and membrane trafficking. Annu. Rev. Cell Dev. Biol. 1998;14:231–264. doi: 10.1146/annurev.cellbio.14.1.231. PubMed DOI

Scharenberg A.M., El-Hillal O., Fruman D.A., Beitz L.O., Li Z.M., Lin S.Q., Gout I., Cantley L.C., Rawlings D.J., Kinet J.P. Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P-3) Tec kinase-dependent calcium signaling pathway: A target for SHIP-mediated inhibitory signals. EMBO J. 1998;17:1961–1972. doi: 10.1093/emboj/17.7.1961. PubMed DOI PMC

Simonsen A., Wurmser A.E., Emr S.D., Stenmark H. The role of phosphoinositides in membrane transport. Curr. Opin. Cell Biol. 2001;13:485–492. doi: 10.1016/S0955-0674(00)00240-4. PubMed DOI

Takenawa T., Itoh T. Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane. Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids. 2001;1533:190–206. doi: 10.1016/S1388-1981(01)00165-2. PubMed DOI

Di Paolo G., De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006;443:651–657. doi: 10.1038/nature05185. PubMed DOI

Delage E., Puyaubert J., Zachowski A., Ruelland E. Signal transduction pathways involving phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: Convergences and divergences among eukaryotic kingdoms. Prog. Lipid Res. 2013;52:1–14. doi: 10.1016/j.plipres.2012.08.003. PubMed DOI

Yoshida S., Ohya Y., Goebl M., Nakano A., Anraku Y. A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae. J. Biol. Chem. 1994;269:1166–1172. PubMed

Cutler N.S., Heitman J., Cardenas M.E. STT4 Is an Essential Phosphatidylinositol 4-Kinase That Is a Target of Wortmannin in Saccharomyces cerevisiae. J. Biol. Chem. 1997;272:27671–27677. doi: 10.1074/jbc.272.44.27671. PubMed DOI

Boronenkov I.V., Anderson R.A. The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases. J. Biol. Chem. 1995;270:2881–2884. doi: 10.1074/jbc.270.7.2881. PubMed DOI

Homma K., Terui S., Minemura M., Qadota H., Anraku Y., Kanaho Y., Ohya Y. Phosphatidylinositol-4-phosphate 5-Kinase Localized on the Plasma Membrane Is Essential for Yeast Cell Morphogenesis. J. Biol. Chem. 1998;273:15779–15786. doi: 10.1074/jbc.273.25.15779. PubMed DOI

McLaughlin S., Wang J., Gambhir A., Murray D. PIP2 and Proteins: Interactions, Organization, and Information Flow. Annu. Rev. Biophys. Biomol. Struct. 2002;31:151–175. doi: 10.1146/annurev.biophys.31.082901.134259. PubMed DOI

Stefan C.J., Audhya A., Emr S.D. The yeast synaptojanin-like proteins control the cellular distribution of phosphatidylinositol (4,5)-bisphosphate. Mol. Biol. Cell. 2002;13:542–557. doi: 10.1091/mbc.01-10-0476. PubMed DOI PMC

Riggi M., Niewola-Staszkowska K., Chiaruttini N., Colom A., Kusmider B., Mercier V., Soleimanpour S., Stahl M., Matile S., Roux A., et al. Decrease in plasma membrane tension triggers PtdIns(4,5)P2 phase separation to inactivate TORC2. Nat. Cell Biol. 2018;20:1043–1051. doi: 10.1038/s41556-018-0150-z. PubMed DOI PMC

Tomioku K.n., Shigekuni M., Hayashi H., Yoshida A., Futagami T., Tamaki H., Tanabe K., Fujita A. Nanoscale domain formation of phosphatidylinositol 4-phosphate in the plasma and vacuolar membranes of living yeast cells. Eur. J. Cell Biol. 2018;97:269–278. doi: 10.1016/j.ejcb.2018.03.007. PubMed DOI

Vernay A., Schaub S., Guillas I., Bassilana M., Arkowitz R.A. A steep phosphoinositide bis-phosphate gradient forms during fungal filamentous growth. J. Cell Biol. 2012;198:711–730. doi: 10.1083/jcb.201203099. PubMed DOI PMC

Hairfield M.L., Westwater C., Dolan J.W. Phosphatidylinositol-4-phosphate 5-kinase activity is stimulated during temperature-induced morphogenesis in Candida albicans. Microbiology. 2002;148:1737–1746. doi: 10.1099/00221287-148-6-1737. PubMed DOI

Rozelle A.L., Machesky L.M., Yamamoto M., Driessens M.H.E., Insall R.H., Roth M.G., Luby-Phelps K., Marriott G., Hall A., Yin H.L. Phosphatidylinositol 4,5-bisphosphate induces actin-based movement of raft-enriched vesicles through WASP-Arp2/3. Curr. Biol. 2000;10:311–320. doi: 10.1016/S0960-9822(00)00384-5. PubMed DOI

Kim Y.J., Guzman-Hernandez M.L., Balla T. A Highly Dynamic ER-Derived Phosphatidylinositol-Synthesizing Organelle Supplies Phosphoinositides to Cellular Membranes. Dev. Cell. 2011;21:813–824. doi: 10.1016/j.devcel.2011.09.005. PubMed DOI PMC

Ziółkowska N.E., Karotki L., Rehman M., Huiskonen J.T., Walther T.C. Eisosome-driven plasma membrane organization is mediated by BAR domains. Nat. Struct. Mol. Biol. 2011;18:854–856. doi: 10.1038/nsmb.2080. PubMed DOI

Bartlett K., Gadila S.K.G., Tenay B., McDermott H., Alcox B., Kim K. TORC2 and eisosomes are spatially interdependent, requiring optimal level of phosphatidylinositol 4, 5-bisphosphate for their integrity. J. Biosci. 2015;40:299–311. doi: 10.1007/s12038-015-9526-4. PubMed DOI

Murphy E.R., Boxberger J., Colvin R., Lee S.J., Zahn G., Loor F., Kim K. Pil1, an eisosome organizer, plays an important role in the recruitment of synaptojanins and amphiphysins to facilitate receptor-mediated endocytosis in yeast. Eur. J. Cell Biol. 2011;90:825–833. doi: 10.1016/j.ejcb.2011.06.006. PubMed DOI

Badrane H., Nguyen M.H., Blankenship J.R., Cheng S., Hao B., Mitchell A.P., Clancy C.J. Rapid Redistribution of Phosphatidylinositol-(4,5)-Bisphosphate and Septins during the Candida albicans Response to Caspofungin. Antimicrob. Agents Chemother. 2012;56:4614–4624. doi: 10.1128/AAC.00112-12. PubMed DOI PMC

Alvarez F.J., Douglas L.M., Rosebrock A., Konopka J.B. The Sur7 Protein Regulates Plasma Membrane Organization and Prevents Intracellular Cell Wall Growth in Candida albicans. Mol. Biol. Cell. 2008;19:5214–5225. doi: 10.1091/mbc.e08-05-0479. PubMed DOI PMC

Kabeche R., Madrid M., Cansado J., Moseley J.B. Eisosomes regulate phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) cortical clusters and mitogen-activated protein (MAP) kinase signaling upon osmotic stress. J. Biol. Chem. 2015;290:25960–25973. doi: 10.1074/jbc.M115.674192. PubMed DOI PMC

Scheek S., Brown M.S., Goldstein J.L. Sphingomyelin depletion in cultured cells blocks proteolysis of sterol regulatory element binding proteins at site 1. Proc. Natl. Acad. Sci. USA. 1997;94:11179–11183. doi: 10.1073/pnas.94.21.11179. PubMed DOI PMC

Beeler T., Bacikova D., Gable K., Hopkins L., Johnson C., Slife H., Dunn T. The Saccharomyces cerevisiae TSC10/YBR265w gene encoding 3-ketosphinganine reductase is identified in a screen for temperature-sensitive suppressors of the Ca2+-sensitive csg2 Delta mutant. J. Biol. Chem. 1998;273:30688–30694. doi: 10.1074/jbc.273.46.30688. PubMed DOI

Baudry K., Swain E., Rahier A., Germann M., Batta A., Rondet S., Mandala S., Henry K., Tint G.S., Edlind T., et al. The effect of the erg26-1 mutation on the regulation of lipid metabolism in Saccharomyces cerevisiae. J. Biol. Chem. 2001;276:12702–12711. doi: 10.1074/jbc.M100274200. PubMed DOI

Eisenkolb M., Zenzmaier C., Leitner E., Schneiter R. A Specific Structural Requirement for Ergosterol in Long-chain Fatty Acid Synthesis Mutants Important for Maintaining Raft Domains in Yeast. Mol. Biol. Cell. 2002;13:4414–4428. doi: 10.1091/mbc.e02-02-0116. PubMed DOI PMC

Swain E., Baudry K., Stukey J., McDonough V., Germann M., Nickels J.T. Sterol-dependent regulation of sphingolipid metabolism in Saccharomyces cerevisiae. J. Biol. Chem. 2002;277:26177–26184. doi: 10.1074/jbc.M204115200. PubMed DOI

Sano T., Kihara A., Kurotsu F., Iwaki S., Igarashi Y. Regulation of the sphingoid long-chain base kinase Lcb4p by ergosterol and heme - Studies in phytosphingosine-resistant mutants. J. Biol. Chem. 2005;280:36674–36682. doi: 10.1074/jbc.M503147200. PubMed DOI

Valachovic M., Wilcox L.J., Sturley S.L., Bard M. A mutation in sphingolipid synthesis suppresses defects in yeast ergosterol metabolism. Lipids. 2004;39:747–752. doi: 10.1007/s11745-004-1291-6. PubMed DOI

Valachovic M., Bareither B.M., Bhuiyan M.S.A., Eckstein J., Barbuch R., Balderes D., Wilcox L., Sturley S.L., Dickson R.C., Bard M. Cumulative Mutations Affecting Sterol Biosynthesis in the Yeast Saccharomyces cerevisiae Result in Synthetic Lethality That Is Suppressed by Alterations in Sphingolipid Profiles. Genetics. 2006;173:1893–1908. doi: 10.1534/genetics.105.053025. PubMed DOI PMC

Brice S.E., Alford C.W., Cowart L.A. Modulation of sphingolipid metabolism by the phosphatidylinositol-4-phosphate phosphatase Sac1p through regulation of phosphatidylinositol in Saccharomyces cerevisiae. J. Biol. Chem. 2009;284:7588–7596. doi: 10.1074/jbc.M808325200. PubMed DOI PMC

Carman G.M., Han G.-S. Phosphatidic Acid Phosphatase, a Key Enzyme in the Regulation of Lipid Synthesis. J. Biol. Chem. 2009;284:2593–2597. doi: 10.1074/jbc.R800059200. PubMed DOI PMC

Guan X.L., Souza C.M., Pichler H., Schaad O., Kajiwara K., Wakabayashi H., Ivanova T., Castillon G.A., Piccolis M., Abe F., et al. Functional Interactions between Sphingolipids and Sterols in Biological Membranes Regulating Cell Physiology. Mol. Biol. Cell. 2009;20:2083–2095. doi: 10.1091/mbc.e08-11-1126. PubMed DOI PMC

Raychaudhuri S., Im Y.J., Hurley J.H., Prinz W.A. Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides. J. Cell Biol. 2006;173:107–119. doi: 10.1083/jcb.200510084. PubMed DOI PMC

Schulz T.A., Choi M.G., Raychaudhuri S., Mears J.A., Ghirlando R., Hinshaw J.E., Prinz W.A. Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues. J. Cell Biol. 2009;187:889–903. doi: 10.1083/jcb.200905007. PubMed DOI PMC

De Saint-Jean M., Delfosse V., Douguet D., Chicanne G., Payrastre B., Bourguet W., Antonny B., Drin G. Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers. J. Cell Biol. 2011;195:965–978. doi: 10.1083/jcb.201104062. PubMed DOI PMC

Stefan C.J., Manford A.G., Baird D., Yamada-Hanff J., Mao Y., Emr S.D. Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites. Cell. 2011;144:389–401. doi: 10.1016/j.cell.2010.12.034. PubMed DOI

Guo S., Stolz L.E., Lemrow S.M., York J.D. SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J. Biol. Chem. 1999;274:12990–12995. doi: 10.1074/jbc.274.19.12990. PubMed DOI

Hughes W.E., Woscholski R., Cooke F.T., Patrick R.S., Dove S.K., McDonald N.Q., Parker P.J. SAC1 encodes a regulated lipid phosphoinositide phosphatase, defects in which can be suppressed by the homologous Inp52p and Inp53p phosphatases. J. Biol. Chem. 2000;275:801–808. doi: 10.1074/jbc.275.2.801. PubMed DOI

Stradalova V., Blazikova M., Grossmann G., Opekarova M., Tanner W., Malinsky J. Distribution of cortical endoplasmic reticulum determines positioning of endocytic events in yeast plasma membrane. PLoS ONE. 2012;7:e35132. doi: 10.1371/journal.pone.0035132. PubMed DOI PMC

Roelants F.M., Chauhan N., Muir A., Davis J.C., Menon A.K., Levine T.P., Thorner J. TOR complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites. Mol. Biol. Cell. 2018;29:2128–2136. doi: 10.1091/mbc.E18-04-0229. PubMed DOI PMC

Kabeche R., Howard L., Moseley J.B. Eisosomes provide membrane reservoirs for rapid expansion of the yeast plasma membrane. J. Cell Sci. 2015;128:4057–4062. doi: 10.1242/jcs.176867. PubMed DOI PMC

Riggi M., Bourgoint C., Macchione M., Matile S., Loewith R., Roux A. TORC2 controls endocytosis through plasma membrane tension. J. Cell Biol. 2019 doi: 10.1083/jcb.201901096. PubMed DOI PMC

Li L.F., Naseem S., Sharma S., Konopka J.B. Flavodoxin-Like Proteins Protect Candida albicans from Oxidative Stress and Promote Virulence. PLoS Pathog. 2015;11:24. doi: 10.1371/journal.ppat.1005147. PubMed DOI PMC

Desmyter L., Verstraelen J., Dewaele S., Libert C., Contreras R., Chen C. Nonclassical export pathway: Overexpression of NCE102 reduces protein and DNA damage and prolongs lifespan in an SGS1 deficient Saccharomyces cerevisiae. Biogerontology. 2007;8:527–535. doi: 10.1007/s10522-007-9095-5. PubMed DOI

Zhang L.B., Tang L., Ying S.H., Feng M.G. Two eisosome proteins play opposite roles in autophagic control and sustain cell integrity, function and pathogenicity in Beauveria bassiana. Environ. Microbiol. 2017;19:2037–2052. doi: 10.1111/1462-2920.13727. PubMed DOI

Conserved mechanism of Xrn1 regulation by glycolytic flux and protein aggregation

Two Different Phospholipases C, Isc1 and Pgc1, Cooperate To Regulate Mitochondrial Function

Microdomain Protein Nce102 Is a Local Sensor of Plasma Membrane Sphingolipid Balance

Plasma Membrane Protein Nce102 Modulates Morphology and Function of the Yeast Vacuole