Voynova, Natalia S. Mallela, Shamroop K. Vazquez, Hector M. Cerantola, Vanessa Sonderegger, Mélanie Knudsen, Jens Ejsing, Christer S. Conzelmann, Andreas 2014-08-01 Humans and yeast possess alkaline ceramidases located in the early secretory pathway. Single deletions of the highly homologous yeast alkaline ceramidases <em>YPC1</em> and <em>YDC1</em> have very little genetic interactions or phenotypes. Here, we performed chemical-genetic screens to find deletions/conditions that would alter the growth of <em>ypc1∆ydc1∆</em> double mutants. These screens were essentially negative, demonstrating that ceramidase activity is not required for cell growth even under genetic stresses. A previously reported protein targeting defect of <em>ypc1∆</em> could not be reproduced and reported abnormalities in sphingolipid biosynthesis detected by metabolic labeling do not alter the mass spectrometric lipid profile of <em>ypc1∆ydc1∆</em> cells. Ceramides of <em>ypc1∆ydc1∆</em> remained normal even in presence of aureobasidin A, an inhibitor of inositolphosphorylceramide synthase. Moreover, in caloric restriction conditions Ypc1p reduces chronological life span. A novel finding is that, when working backwards as a ceramide synthase <em>in vivo</em>, Ypc1p prefers C24 and C26 fatty acids as substrates, whereas it prefers C16:0, when solubilized in detergent and working <em>in vitro</em>. Therefore, its physiological activity may not only concern the minor ceramides containing C14 and C16. Intriguingly, so far the sole discernable benefit of conserving <em>YPC1</em> for yeast resides with its ability to convey relative resistance toward H₂O₂. application/pdf https://folia.unifr.ch/global/documents/303711 https://folia.unifr.ch/documents/303711/files/con_cym.pdf https://folia.unifr.ch/documents/303711/files/con_sym_sm.pdf https://folia.unifr.ch/documents/303711/files/con_sym_sm2.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1111/1567-1364.12169 info:eu-repo/semantics/openAccess License undefined FEMS Yeast Research. - 2014, vol. 14, no. 5, p. 776–788 info:eu-repo/classification/udc/57 Characterization of yeast mutants lacking alkaline ceramidases YPC1 and YDC1 http://purl.org/coar/resource_type/c_6501