{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:21:11Z","timestamp":1781954471257,"version":"3.54.5"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Inositolphosphorylceramide (IPC) and its mannosylated derivatives are the only complex sphingolipids of yeast. Their synthesis can be reduced by aureobasidin A (AbA), which specifically inhibits the IPC synthase Aur1. AbA reportedly, by diminishing IPC levels, causes endoplasmic reticulum (ER) stress, an increase in cytosolic calcium, reactive oxygen production, and mitochondrial damage leading to apoptosis. We found that when Aur1 is gradually depleted by transcriptional downregulation, the accumulation of ceramides becomes a major hindrance to cell survival. Overexpression of the alkaline ceramidase\n            <jats:italic>YPC1<\/jats:italic>\n            rescues cells under this condition. We established hydroxylated C\n            <jats:sub>26<\/jats:sub>\n            fatty acids as a reliable hallmark of ceramide hydrolysis. Such hydrolysis occurs only when\n            <jats:italic>YPC1<\/jats:italic>\n            is overexpressed. In contrast, overexpression of\n            <jats:italic>YPC1<\/jats:italic>\n            has no beneficial effect when Aur1 is acutely repressed by AbA. A high-throughput genetic screen revealed that vesicle-mediated transport between Golgi apparatus, endosomes, and vacuole becomes crucial for survival when Aur1 is repressed, irrespective of the mode of repression. In addition, vacuolar acidification becomes essential when cells are acutely stressed by AbA, and quinacrine uptake into vacuoles shows that AbA activates vacuolar acidification. The antioxidant\n            <jats:italic>N<\/jats:italic>\n            -acetylcysteine does not improve cell growth on AbA, indicating that reactive oxygen radicals induced by AbA play a minor role in its toxicity. AbA strongly induces the cell wall integrity pathway, but osmotic support does not improve the viability of wild-type cells on AbA. Altogether, the data support and refine current models of AbA-mediated cell death and add vacuolar protein transport and acidification as novel critical elements of stress resistance.\n          <\/jats:p>","DOI":"10.1128\/ec.00117-15","type":"journal-article","created":{"date-parts":[[2015,10,3]],"date-time":"2015-10-03T00:33:15Z","timestamp":1443832395000},"page":"1203-1216","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Saccharomyces cerevisiae Is Dependent on Vesicular Traffic between the Golgi Apparatus and the Vacuole When Inositolphosphorylceramide Synthase Aur1 Is Inactivated"],"prefix":"10.1128","volume":"14","author":[{"given":"Natalia S.","family":"Voynova","sequence":"first","affiliation":[{"name":"Division of Biochemistry, Department of Biology, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Roubaty","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Biology, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector M.","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Biology, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamroop K.","family":"Mallela","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Biology, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer S.","family":"Ejsing","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Conzelmann","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Biology, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.14.4325-4332.1991"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.15.9809"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004380050530"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305498200"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306119200"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.12.2765"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/BF02172923","article-title":"AUR1, a novel gene conferring aureobasidin resistance on Saccharomyces cerevisiae: a study of defective morphologies in Aur1p-depleted cells","volume":"251","author":"Hashida-Okado T","year":"1996","unstructured":"Hashida-Okado T, Ogawa A, Endo M, Yasumoto R, Takesako K, Kato I. 1996. 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