Functional characterization of Hul6 reveals a role in iron-dependent metabolism in Schizosaccharomyces pombe.
Iron is essential for all organisms. In Schizosaccharomyces pombe, the GATA-binding repressor Fep1 and CCAAT-binding repressor Php4 control the expression of iron uptake and iron utilization genes, respectively, and mutually repress each other. We have shown that the E3 ligase Hul6 regulates Php4 target genes through Php4 degradation. Here, we further investigated Hul6 targets. RNA-seq analysis identified 327 differentially expressed genes (DEGs). GO analysis revealed upregulation of iron uptake genes and downregulation of genes involved in iron-dependent metabolism including mitochondrial oxidative phosphorylation (OXPHOS), suggesting an iron starvation-like response in Δhul6 cells. Promoter analysis identified GATA and CCAAT motifs in DEGs, suggesting potential direct targets for Fep1 and Php4, respectively. Furthermore, Δhul6 cells showed reduction in oxygen consumption and mitochondrial membrane potential, further supporting that Hul6 regulates OXPHOS. Our findings extend previous studies and further support a role for Hul6 in the control of iron-dependent metabolism in S. pombe.
Li R, Zhu M, Ashfaq Y, Zhu Y, Fu C, Nawaz Y, Huang Y