UPC2 gene deletion modifies sterol homeostasis and susceptibility to metabolic inhibitors in Kluyveromyces lactis

Kluyveromyces lactis Upc2p is an ortholog of Upc2p/Ecm22p transcription factors involved in regulation of sterol import and sterol homeostasis in Saccharomyces cerevisiae . In this work, we investigated the role of Upc2p in K. lactis . The absence of Kl Upc2p significantly reduced the tolerance of mutant cells to antifungal azoles and Li + cations. Reduced expression of genes from the late ergosterol pathway results in a decreased ergosterol content and altered plasma membrane‐associated functions in Klupc2 mutant cells—the plasma membrane is hyperpolarized, and its fluidity is reduced. Kl Upc2p contributes to transcriptional upregulation of KlENA1 , KlPMA1 and KlYAP1 under azole stress. Our study demonstrates that Kl Upc2p is involved in the regulation of ergosterol homeostasis in K. lactis . The analysis of KlPMA1 and KlPDR12 transcripts in wild‐type and Klupc2Δ mutant strains showed that Kl Upc2p acts as an activator or as a repressor depending upon its target.