title: Quantitative mapping of reversible mitochondrial Complex I cysteine oxidation in a Parkinson disease mouse model.
abstract: Differential cysteine oxidation within mitochondrial Complex I has been quantified in an in vivo oxidative stress model of Parkinson disease. We developed a strategy that incorporates rapid and efficient immunoaffinity purification of Complex I followed by differential alkylation and quantitative detection using sensitive mass spectrometry techniques. This method allowed us to quantify the reversible cysteine oxidation status of 34 distinct cysteine residues out of a total 130 present in murine Complex I. Six Complex I cysteine residues were found to display an increase in oxidation relative to controls in brains from mice undergoing in vivo glutathione depletion. Three of these residues were found to reside within iron-sulfur clusters of Complex I, suggesting that their redox state may affect electron transport function.
authors.affiliation: Buck Institute for Age Research, Novato, California 94945, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Danielson
authors.forename: Jason M
authors.initials: JM
authors.lastname: Held
authors.forename: May
authors.initials: M
authors.lastname: Oo
authors.forename: Rebeccah
authors.initials: R
authors.lastname: Riley
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Gibson
authors.forename: Julie K
authors.initials: JK
authors.lastname: Andersen
mesh_terms: D000478:Alkylation; D000818:Animals; D003461:Crystallography; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007118:Immunoassay; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology*; D009410:Nerve Degeneration / Q000378:metabolism; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D042967:Electron Transport Complex I; D005978:Glutathione; D003545:Cysteine