Transcriptional regulation of ergosterol biosynthesis genes in response to iron deficiency

• Published in: Environmental microbiology Vol. 24; no. 11; pp. 5248 - 5260
• Main Authors: Jordá, Tania, Barba‐Aliaga, Marina, Rozès, Nicolas, Alepuz, Paula, Martínez‐Pastor, María Teresa, Puig, Sergi
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2022; Wiley Subscription Services, Inc
• Subjects: Antifungal Agents - metabolism; Availability; Biosynthesis; Deoxyribonucleic acid; DNA; Ergosterol; Ergosterol - metabolism; Fungicides; Gene Expression Regulation, Fungal; Gene regulation; Gene silencing; Genes; Heme; Heme - metabolism; Humans; Intermediates; Iron; Iron - metabolism; Iron Deficiencies; Iron deficiency; Lipids; Nutrient deficiency; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sterols; Transcription; Transcription activation; Transcription factors; Transcription Factors - genetics; Yeast; Yeasts
• ISSN: 1462-2912; 1462-2920; 1462-2920
• DOI: 10.1111/1462-2920.16157

Iron participates as an essential cofactor in the biosynthesis of critical cellular components, including DNA, proteins and lipids. The ergosterol biosynthetic pathway, which is an important target of antifungal treatments, depends on iron in four enzymatic steps. Our results in the model yeast Saccharomyces cerevisiae show that the expression of ergosterol biosynthesis (ERG) genes is tightly modulated by iron availability probably through the iron‐dependent variation of sterol and heme levels. Whereas the transcription factors Upc2 and Ecm22 are responsible for the activation of ERG genes upon iron deficiency, the heme‐dependent factor Hap1 triggers their Tup1‐mediated transcriptional repression. The combined regulation by both activating and repressing regulatory factors allows for the fine‐tuning of ERG transcript levels along the progress of iron deficiency, avoiding the accumulation of toxic sterol intermediates and enabling efficient adaptation to rapidly changing conditions. The lack of these regulatory factors leads to changes in the yeast sterol profile upon iron‐deficient conditions. Both environmental iron availability and specific regulatory factors should be considered in ergosterol antifungal treatments.