title: KlMID1, a relevant key player between endoplasmic reticulum homeostasis and mitochondrial dysfunction in Kluyveromyces lactis.
abstract: The interplay between calcium metabolism and glycosylation in yeast is largely unknown. In order to clarify this relationship, the effect of a mutation in the KlOCH1 gene, encoding the Golgi α-1,6-mannosyltransferase, on calcium homeostasis was studied in the yeast Kluyveromyces lactis. In particular, the role of the KlMID1 gene, encoding one of the components of the plasma membrane calcium channel (Cch1-Mid1), was investigated. Almost complete suppression of the phenotypes occurring in the mutant strain, ranging from oxidative stress to cell wall alteration, was observed by increased dosage of KlMID1. In addition, the N-glycosylation mutant showed increased calcium accumulation and decreased transcription of KlMID1 and KlCCH1. Moreover, the calcium alterations included an increased expressional profile for the KlPMC1 gene, encoding the vacuolar calcium ion pump. Furthermore, perturbation of endoplasmic reticulum (ER) homeostasis was observed in Kloch1-1 cells. Similarly, down-modulation of calcium signalling genes as well as altered mitochondrial functionality were induced in wild-type cells after treatment with DTT. However, no mitochondrial alteration occurred in the treated cells when KlMID1 was overexpressed. Our results suggest that the ER stress taking place in Kloch1-1 cells appears to be the primary cause of the KlMID1 down-modulation and its resulting effects on the expression of calcium homeostasis genes.
authors.affiliation: Department Biology and Biotechnology University of Rome LA SAPIENZA, 00185 Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zanni
authors.affiliation: Department Biology and Biotechnology University of Rome LA SAPIENZA, 00185 Rome, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Franco
authors.affiliation: Department Biology, Tokyo Gakugei University, Koganei-shi, Tokyo 184-8501, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department Biology, Tokyo Gakugei University, Koganei-shi, Tokyo 184-8501, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department Biology and Biotechnology University of Rome LA SAPIENZA, 00185 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Palleschi
authors.affiliation: Department Biology and Biotechnology University of Rome LA SAPIENZA, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Uccelletti
mesh_terms: D015220:Calcium Channels / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017353:Gene Deletion; D018628:Gene Dosage; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D007716:Kluyveromyces / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D015220:Calcium Channels