Increased heme synthesis in yeast induces a metabolic switch from fermentation to respiration even under conditions of glucose repression

• DOI: 10.1074/jbc.m117.790923
• Publication Date: 2017-08-23T00:55:21Z
• Authors: Tiantian Zhang; Pengli Bu; Joey Zeng; Ales Vancura
• Keywords: Cellular respiration

Regulation of mitochondrial biogenesis and respiration is a complex process that involves several signaling pathways transcription factors as well communication between the nuclear genomes. Under aerobic conditions, budding yeast Saccharomyces cerevisiae metabolizes glucose predominantly by glycolysis fermentation. We have recently shown altered chromatin structure in induces mechanism requires transport metabolism pyruvate mitochondria. However, how controls transcriptional responses underlying metabolic switch from fermentation to unknown. Here, we report this effect heme. found heme HAP4, activation subunit Hap2/3/4/5p complex, required for growth on nonfermentable carbon sources, Hap1p- Hap2/3/4/5p-dependent manner. Increasing cellular levels inactivating ROX1, which encodes repressor many hypoxic genes, or overexpressing HEM3 HEM12 induced elevated ATP levels. Increased synthesis, even under conditions repression, activated Hap1p HAP4 genes tricarboxylic acid (TCA) cycle, electron chain, oxidative phosphorylation, leading respiration. Conversely, inhibiting flux into TCA cycle reduced transcription. Together, our results indicate glucose-mediated repression at least partly due low level.