title: Aspergillus oryzae flavohemoglobins promote oxidative damage by hydrogen peroxide.
abstract: Apart from their well-established role in nitric oxide detoxification, flavohemoglobins (FHbs) are also believed to be involved in protection against oxidative stress in some yeast and bacteria. However, different studies have reported contradictory results in this regard. Here, we investigate the relationship between two FHbs in Aspergillus oryzae (cytosolic FHb1 and mitochondrial FHb2) and oxidative stress. The strains deficient in the two FHbs exhibited higher resistance to hydrogen peroxide than the wild-type. In addition, the FHb2 overexpression strain showed hypersensitivity to hydrogen peroxide. Flavin reductase accompanied by the ferric reductase activities of the two FHbs were observed in correspondence with this expression. The reductase activities of the FHbs were attributed to their C-terminal flavin reductase domains. The reduced intracellular free iron can subsequently promote oxidative damage by accelerating the Fenton reaction in the cytosol and mitochondria (corresponding to the subcellular localizations of the two FHbs). This study is the first to show that fungal FHbs have a deleterious effect on oxidative protection, and suggests that the accelerated Fenton reaction induced by FHbs might be responsible for this effect.
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Zhou
authors.forename: Shinya
authors.initials: S
authors.lastname: Fushinobu
authors.forename: Sang-Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Wakagi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shoun
mesh_terms: D001236:Aspergillus oryzae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D007501:Iron / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: C045076:Fenton's reagent; D006420:Hemeproteins; D006861:Hydrogen Peroxide; D007501:Iron