title: Determination of the oxidation states of manganese in brain, liver, and heart mitochondria.
abstract: Excess brain manganese can produce toxicity with symptoms that resemble those of Parkinsonism and causes that remain elusive. Manganese accumulates in mitochondria, a major source of superoxide, which can oxidize Mn2+ to the powerful oxidizing agent Mn3+. Oxidation of important cell components by Mn3+ has been suggested as a cause of the toxic effects of manganese. Determining the oxidation states of intramitochondrial manganese could help to identify the dominant mechanism of manganese toxicity. Using X-ray absorbance near edge structure (XANES) spectroscopy, we have characterized the oxidation state of manganese in mitochondria isolated from brain, liver, and heart over concentrations ranging from physiological to pathological. Results showed that (i) spectra from different model manganese complexes of the same oxidation state were similar to each other and different from those of other oxidation states and that the position of the absorption edge increases with oxidation state; (ii) spectra from intramitochondrial manganese in isolated brain, heart and liver mitochondria were virtually identical; and (iii) under these conditions intramitochondrial manganese exists primarily as a combination of Mn2+ complexes. No evidence for Mn3+ was detected in samples containing more than endogenous manganese levels, even after incubation under conditions promoting reactive oxygen species (ROS) production. While the presence of Mn3+ complexes cannot be proven in the spectrum of endogenous mitochondrial manganese, the shape of this spectrum could suggest the presence of Mn3+ near the limit of detection, probably as MnSOD.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester, School of Medicine and Dentistry, Rochester, New York 14642, USA. thomas_gunter@urmc.rochester.edu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Gunter
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Miller
authors.forename: Claire E
authors.initials: CE
authors.lastname: Gavin
authors.forename: Roman
authors.initials: R
authors.lastname: Eliseev
authors.forename: Jason
authors.initials: J
authors.lastname: Salter
authors.forename: Linas
authors.initials: L
authors.lastname: Buntinas
authors.forename: Andrei
authors.initials: A
authors.lastname: Alexandrov
authors.forename: Sean
authors.initials: S
authors.lastname: Hammond
authors.forename: Karlene K
authors.initials: KK
authors.lastname: Gunter
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D002645:Chickens; D008345:Manganese / Q000032:analysis* / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000737:chemistry / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission / Q000379:methods
chemical_list: D017382:Reactive Oxygen Species; D008345:Manganese