title: The overlapping roles of manganese and Cu/Zn SOD in oxidative stress protection.
abstract: In various organisms, high intracellular manganese provides protection against oxidative damage through unknown pathways. Herein we use a genetic approach in Saccharomyces cerevisiae to analyze factors that promote manganese as an antioxidant in cells lacking Cu/Zn superoxide dismutase (sod1 Delta). Unlike certain bacterial systems, oxygen resistance in yeast correlates with high intracellular manganese without a lowering of iron. This manganese for antioxidant protection is provided by the Nramp transporters Smf1p and Smf2p, with Smf1p playing a major role. In fact, loss of manganese transport by Smf1p together with loss of the Pmr1p manganese pump is lethal to sod1 Delta cells despite normal manganese SOD2 activity. Manganese-phosphate complexes are excellent superoxide dismutase mimics in vitro, yet through genetic disruption of phosphate transport and storage, we observed no requirement for phosphate in manganese suppression of oxidative damage. If anything, elevated phosphate correlated with profound oxidative stress in sod1 Delta mutants. The efficacy of manganese as an antioxidant was drastically reduced in cells that hyperaccumulate phosphate without effects on Mn SOD activity. Non-SOD manganese can provide a critical backup for Cu/Zn SOD1, but only under appropriate physiologic conditions.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Amit R
authors.initials: AR
authors.lastname: Reddi
authors.forename: Laran T
authors.initials: LT
authors.lastname: Jensen
authors.forename: Amornrat
authors.initials: A
authors.lastname: Naranuntarat
authors.forename: Leah
authors.initials: L
authors.lastname: Rosenfeld
authors.forename: Edison
authors.initials: E
authors.lastname: Leung
authors.forename: Rishita
authors.initials: R
authors.lastname: Shah
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Culotta
mesh_terms: D000332:Aerobiosis / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017895:Manganese Compounds / Q000494:pharmacology; D018832:Molecular Chaperones; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D000252:Calcium-Transporting ATPases; D027682:Cation Transport Proteins; D016166:Free Radical Scavengers; D017895:Manganese Compounds; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C495386:BSD2 protein, S cerevisiae; C105116:SMF1 protein, S cerevisiae; C101767:SSC1 protein, S cerevisiae; C416343:Smf2 protein, S cerevisiae