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Title (Primary) ER stress induced by the OCH1 mutation triggers changes in lipid homeostasis in Kluyveromyces lactis
Author Zanni, E.; Maulucci, G.; Pomata, D.; Buiarelli, F.; Krasnowska, E.K.; Parasassi, T.; De Spirito, M.; Heipieper, H.J.; Uccelletti, D.;
Journal Research in Microbiology
Year 2015
Department UBT;
Volume 166
Issue 2
Language englisch;
POF III (all) T41;
Keywords Fatty acids; Lipid droplets; 4-PBA; N-glycosylation; ER stress
UFZ wide themes RU3;
Abstract In Kluyveromyces lactis yeast, OCH1 encodes for the α-1,6-mannosyltrasferase that adds the initial α-1,6-mannose to the outer-chains of N-glycoproteins. Kloch1-1 mutant cells showed altered calcium homeostasis and endoplasmic reticulum (ER) stress. Since ER plays a major role in lipid biosynthesis and lipid droplet (LD) formation, herein the impact of Och1p depletion on lipid homeostasis was investigated. Transcriptional profiles of genes involved in biosynthesis of fatty acids, their amount and composition changed in mutant cells. An increased amount of ergosterol was determined in these cells. Enhanced transcription of genes involved in both synthesis and mobilization of LDs was also found in Kloch1-1 cells, accompanied by a reduced amount of LDs. We provide evidence that ER alterations, determined by protein misfolding as a result of reduced N-glycosylation, induced altered lipid homeostasis in Kloch1-1 cells. Chemical chaperone 4-phenyl butyrate (4-PBA) slightly alleviated the LD phenotype in cells depleted of Och1p. Remarkably, complete suppression of ER stress, via increased expression of plasma membrane calcium channel subunit Mid1, fully restored lipid homeostasis in mutant cells. To further reinforce this finding, low numbers of LDs were observed in wild type cells when ER stress was triggered by DTT treatment.
ID 15778
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=15778
Zanni, E., Maulucci, G., Pomata, D., Buiarelli, F., Krasnowska, E.K., Parasassi, T., De Spirito, M., Heipieper, H.J., Uccelletti, D. (2015):
ER stress induced by the OCH1 mutation triggers changes in lipid homeostasis in Kluyveromyces lactis
Res. Microbiol. 166 (2), 84 - 92