title: Manganese complexes: diverse metabolic routes to oxidative stress resistance in prokaryotes and yeast.
abstract: CONCLUSIONS
  Antioxidant enzymes are thought to provide critical protection to cells against reactive oxygen species (ROS). However, many organisms can fully compensate for the loss of such enzymatic defenses by accumulating metabolites and Mn²⁺, which can form catalytic Mn-antioxidants. Accumulated metabolites can direct reactivity of Mn²⁺ with superoxide and specifically shield proteins from oxidative damage.
  
  
  BACKGROUND
  There is mounting evidence that Mn-Pi (orthophosphate) complexes act as potent scavengers of superoxide in all three branches of life. Moreover, it is evident that Mn²⁺ in complexes with carbonates, peptides, nucleosides, and organic acids can also form catalytic Mn-antioxidants, pointing to diverse metabolic routes to oxidative stress resistance.
  
  
  RESULTS
  What conditions favor utility of Mn-metabolites versus enzymatic means for removing ROS? Mn²⁺-metabolite defenses are critical for preserving the activity of repair enzymes in Deinococcus radiodurans exposed to intense radiation stress, and in Lactobacillus plantarum, which lacks antioxidant enzymes. In other microorganisms, Mn-antioxidants can serve as an auxiliary protection when enzymatic antioxidants are insufficient or fail. These findings of a critical role of Mn-antioxidants in the survival of prokaryotes under oxidative stress parallel the trends developing for the simple eukaryote Saccharomyces cerevisiae.
  
  
  CONCLUSIONS
  Phosphates, peptides and organic acids are just a snapshot of the types of anionic metabolites that promote such reactivity of Mn²⁺. Their probable roles in pathogen defense against the host immune response and in ROS-mediated signaling pathways are also areas that are worthy of serious investigation. Moreover, it is clear that these protective chemical processes can be harnessed for practical purposes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. vculotta@jhsph.edu
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Culotta
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Daly
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism; D008345:Manganese / Q000737:chemistry / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011387:Prokaryotic Cells / Q000378:metabolism; D011836:Radiation Tolerance; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010455:Peptides; D008345:Manganese; D013482:Superoxide Dismutase