Yeast flavin-containing monooxygenase is induced by the unfolded protein response

Flavin-containing monooxygenase from yeast (yFMO) carries out the O-2- and NADPH-dependent oxidation of biological thiols, including oxidizing glutath ione to glutathione disulfide, FMO provides a large fraction of the oxidizi ng necessary for proper folding of disulfide bond-containing proteins; dele tion of the enzyme reduces proper folding of endogenous carboxypeptidase Y by about 40%, The enzyme is not essential to cell viability because other e nzymes can generate a significant fraction of the oxidizing equivalents req uired by the cell. However, yFMO is vital to the yeast response to reductiv e stress. FMO1 deletion mutants grow poorly under reductive stress, and car boxypeptidase Y activity is less than 10% of that in a stressed wild type. The FMO1 gene appears to be under control of an unfolded protein response e lement and is inducible by factors, such as reductive stress, that elicit t he unfolded protein response. Reductive stress can increase yFMO activity a t least 6-fold. This increased activity allows the cell to process endogeno us disulfide bond-containing proteins and also to allow correct folding of disulfide-bonded proteins expressed from multicopy plasmids, The unfolded p rotein response is mediated by the Hac1p transcription factor that mediates virtually all of the induction of yFMO triggered by exogenous reducing age nts.