Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine

Simone Beretta, Gessica Sala, Laura Mattavelli, Chiara Ceresa, Arianna Casciati, Alberto Ferri, Maria Teresa Carrì, Carlo Ferrarese

Research output: Contribution to journalArticle

Abstract

We report that the expression of mutant G93A copper/zinc superoxide dismutase (SOD1), associated with familial amyotrophic lateral sclerosis, specifically causes a decrease in MTT reduction rate and ATP levels and an increase in both cytosolic and mitochondrial reactive oxygen species (ROS) production in human neuroblastoma SH-SY5Y cells compared to cells overexpressing wild-type SOD1 and untransfected cells. Exposure to N-acetylcysteine lowers ROS production and returns mitochondrial functional assays to control levels. No large aggregates of human SOD1 are detectable under basal growth conditions in any of the investigated cell lines. After proteasome activity inhibition, SOD1 aggregates can be detected exclusively in G93A-SOD1 cells, even though they do not per se enhance cell death compared to control cell lines. Our findings indicate that mitochondrial homeostasis is affected by mutant SOD1-generated ROS independently from the formation of aggregates and that this alteration is reversed by antioxidants.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalNeurobiology of Disease
Volume13
Issue number3
DOIs
Publication statusPublished - Aug 2003

Fingerprint

Amyotrophic Lateral Sclerosis
Acetylcysteine
Superoxide Dismutase
Zinc
Copper
Reactive Oxygen Species
Cell Line
Proteasome Endopeptidase Complex
Neuroblastoma
Homeostasis
Cell Death
Antioxidants
Adenosine Triphosphate
Growth

Keywords

  • Amyotrophic lateral sclerosis
  • Mitochondrial function
  • N-Acetylcysteine
  • Oxidative stress
  • SOD1

ASJC Scopus subject areas

  • Neurology

Cite this

Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine. / Beretta, Simone; Sala, Gessica; Mattavelli, Laura; Ceresa, Chiara; Casciati, Arianna; Ferri, Alberto; Carrì, Maria Teresa; Ferrarese, Carlo.

In: Neurobiology of Disease, Vol. 13, No. 3, 08.2003, p. 213-221.

Research output: Contribution to journalArticle

Beretta, Simone ; Sala, Gessica ; Mattavelli, Laura ; Ceresa, Chiara ; Casciati, Arianna ; Ferri, Alberto ; Carrì, Maria Teresa ; Ferrarese, Carlo. / Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine. In: Neurobiology of Disease. 2003 ; Vol. 13, No. 3. pp. 213-221.
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