Role in anaerobiosis of the isoenzymes for Saccharomyces cerevisiae fumarate reductase encoded by OSM1 and FRDS1.
Saccharomyces cerevisiae possesses both a cytoplasmic and a mitochondrial fumarate reductase, encoded by FRDS1 and OSM1, respectively. While previous studies have shown that mutants lacking FRDS1 and OSM1 cannot grow under anaerobiosis (Arikawa et al., 1998), the physiological role of fumarate reductase (FR) remains poorly understood. Here, we report that an osm1 frds1 mutant is unable to grow anaerobically, even with glutamate as a sole nitrogen source, when succinate can be produced by the TCA oxidative branch. We also show that the growth of the mutant is not restored by adding acetoin, an alternative sink for NADH oxidation, but it is at least partly restored by the addition of oxygen or menadione, which can oxidize FADH(2) in addition to NADH. These data indicate that the growth inhibition of the mutant is due to an inability to reoxidize FAD, rather than an indirect effect on NADH or an inability to produce succinate per se. During anaerobic growth, FRDS1 expression was two to eight times higher than that of OSM1, and fumarate reductase activity was higher in the osm1 mutant than in the frds1 mutant. FRDS1 expression was induced by anaerobiosis, and this induction was abolished in a rox1 mutant. We conclude that the formation of succinate is strictly required for the reoxidation of FADH(2) during anaerobiosis, and that it is regulated through the control of FRDS1 expression when oxygen is limiting. Based on these data, we discuss the potential role of fumarate reductase in the regeneration of the FAD-prosthetic group of essential flavoproteins.
Camarasa
Carole
C
UMR1083 Sciences pour l'Oenologie, INRA, 2 Place Viala, F-34060 Montpellier, France. camarasa@ensam.inra.fr
Faucet
Virginie
V
Dequin
Sylvie
S
D000093:Acetoin / Q000494:pharmacology; D000693:Anaerobiosis; D015152:Blotting, Northern; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D010084:Oxidation-Reduction; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019802:Succinic Acid / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology
D007527:Isoenzymes; D012331:RNA, Fungal; D005182:Flavin-Adenine Dinucleotide; D024483:Vitamin K 3; D019802:Succinic Acid; D000093:Acetoin; D013385:Succinate Dehydrogenase