The activator/repressor Hap1 binds to the yeast eIF5A-encoding gene TIF51A to adapt its expression to the mitochondrial functional status

Mitochondrial activity adapts to cellular energetic and metabolic demands; its dysfunction is a hallmark of ageing and many human diseases. The evolutionarily conserved translation elongation factor eIF5A is involved in maintaining mitochondrial function. In humans, eIF5A is encoded by two highly homologous but differentially expressed genes; in yeast, these are TIF51A and TIF51B. We show that yeast transcription factor Hap1 constitutively binds to the TIF51A promoter to activate its expression under respiration, but represses its expression under nonrespiration conditions by recruiting the corepressor Tup1. Hap1 indirectly regulates TIF51B expression by binding to and activating the TIF51B repressor genes ROX1 and MOT3 under respiration and repressing them under nonrespiration. Thus, the levels of eIF5A isoforms are adapted to the mitochondrial functional status.