ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import

摘要: Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords rats and mice expressing mutations. Two-dimensional gels multidimensional liquid chromatography, combination tandem mass spectrometry, revealed 33 proteins that were increased 21 decreased SOD1G93A rat cord compared SOD1WT mitochondria. Analysis this group a higher-than-expected proportion involved complex I protein import pathways. Direct assays 30% decrease only mitochondria, despite an increase mitochondrial components TOM20, TOM22, TOM40. Recombinant or SOD1G85R, but not Parkinson's disease-causing, misfolded α-synucleinE46K mutant, by >50% nontransgenic cord, liver. Thus, altered content accompanied selective decreases into comprises part damage arising mutant SOD1.