Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials

Alberto Ferri, Mauro Cozzolino, Claudia Crosio, Monica Nencini, Arianna Casciati, Edith Butler Gralla, Giuseppe Rotilio, Joan Selverstone Valentine, Maria Teresa Carri

Research output: Contribution to journalArticle


Recent studies suggest that the toxicity of familial amyotrophic lateral sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective recruitment to mitochondria. Here we demonstrate that each of 12 different familial ALS-mutant SOD1s with widely differing biophysical properties are associated with mitochondria of motoneuronal cells to a much greater extent than wild-type SOD1, and that this effect may depend on the oxidation of Cys residues. We demonstrate further that mutant SOD1 proteins associated with the mitochondria tend to form cross-linked oligomers and that their presence causes a shift in the redox state of these organelles and results in impairment of respiratory complexes. The observation that such a diverse set of mutant SOD1 proteins behave so similarly in mitochondria of motoneuronal cells and so differently from wild-type SOD1 suggests that this behavior may explain the toxicity of ALS-mutant SOD1 proteins, which causes motor neurons to die.

Original languageEnglish
Pages (from-to)13860-13865
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
Publication statusPublished - Sep 12 2006


  • Amyotrophic lateral sclerosis
  • Motor neuron
  • Neurodegeneration

ASJC Scopus subject areas

  • Genetics
  • General

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