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Identification of FLC family of proteins required for import of FAD into the endoplasmic reticulum in a screen for heme uptake genes
Author(s) -
Protchenko Olga,
Androphy Rachel,
RodriguezSuarez Roberto,
Bussey Howard,
Protchenko Caroline C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a244-a
Subject(s) - endoplasmic reticulum , saccharomyces cerevisiae , heme , biochemistry , candida albicans , biology , gene , microbiology and biotechnology , chemistry , genetics , enzyme
Candida albicans and Saccharomyces cerevisiae have similar systems of iron uptake but differ in uptake of heme. C. albicans can use heme as the sole source of iron, while S. cerevisiae grows poorly on these media. We identified a gene from C. albicans that would enhance heme uptake when expressed in S. cerevisiae. Overexpression of CaFLC1 (for flavin carrier 1) stimulated the growth of S. cerevisiae on media containing heme iron. The S. cerevisiae genome contains three genes with homology to CaFLC1, and two of these, termed FLC1 and FLC2, also stimulated growth on heme when overexpressed in S. cerevisiae. The S. cerevisiae Flc proteins were detected in the endoplasmic reticulum and the FLC genes encoded an essential function, as deletion of both FLC1 and FLC2 was synthetically lethal. FLC gene deletion resulted in pleiotropic phenotypes. FLC deletion strains exhibited activation of unfolded protein response, defects in cell wall assembly, and delayed maturation of carboxypeptidase Y. Permeabilized cells lacking FLC proteins exhibited dramatic loss of flavin adenine dinucleotide (FAD) import activity. Also, overexpression of FAD1, coding for FAD synthetase, partially restored growth of FLC deleted strain. We propose that the FLC genes are required for import of FAD into the lumen of the endoplasmic reticulum, where it is required for disulfide bond formation.