Interaction between the reductase Tah18 and highly conserved Fe‐S containing Dre2 C‐terminus is essential for yeast viability

SummaryTah18–Dre2 is a recently identified yeast protein complex, which is highly conserved in human and has been implicated in the regulation of oxidative stress induced cell death and in cytosolic Fe‐S proteins synthesis. Tah18 is a diflavin oxido‐reductase with binding sites for flavin mononucleotide, flavin adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, which is able to transfer electrons to Dre2 Fe‐S clusters. In this work we characterized in details the interaction between Tah18 and Dre2, and analysed how it conditions yeast viability. We show that Dre2 C‐terminus interacts in vivo and in vitro with the flavin mononucleotide‐ and flavin adenine dinucleotide‐binding sites of Tah18. Neither the absence of the electron donor nicotinamide adenine dinucleotide phosphate‐binding domain in purified Tah18 nor the absence of Fe‐S in aerobically purified Dre2 prevents the binding in vitro. In vivo, when this interaction is affected in a dre2 mutant, yeast viability is reduced. Conversely, enhancing artificially the interaction between mutated Dre2 and Tah18 restores cellular viability despite still reduced cytosolic Fe‐S cluster biosynthesis. We conclude that Tah18–Dre2 interaction in vivo is essential for yeast viability. Our study may provide new insight into the survival/death switch involving this complex in yeast and in human cells.