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Citation
Bahadorani, S., Mukai, S.T., Rabie, J., Beckman, J.S., Phillips, J.P., Hilliker, A.J. (2013). Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction.  Neurobiol. Aging 34(10): 2322--2330.
FlyBase ID
FBrf0222045
Publication Type
Research paper
Abstract

More than 130 different mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been associated with amyotrophic lateral sclerosis but the mechanism of this toxicity remains controversial. To gain insight into the importance of the zinc site in the pathogenesis of SOD1 in vivo, we generated a Drosophila model with transgenic expression of a zinc-deficient human SOD1. Expression of zinc-deficient SOD1 in Drosophila resulted in a progressive movement defect with associated mitochondrial cristae vacuolization and reductions in adenosine triphosphate (ATP) levels. Furthermore, these flies are sensitized to mitochondrial toxins, paraquat, and zinc. Importantly, we show that the zinc-deficient SOD1-induced motor defect can be ameliorated by supplementing the endogenous fly respiratory chain machinery with the single-subunit NADH-ubiquinone oxidoreductase from yeast (NADH is nicotinamide adenine dinucleotide, reduced form.). These results demonstrate that zinc-deficient SOD1 is neurotoxic in vivo and suggest that mitochondrial dysfunction plays a critical role in this toxicity. The robust behavioral, pathological, and biochemical phenotypes conferred by zinc-deficient SOD1 in Drosophila have general implications for the role of the zinc ion in familial and sporadic amyotrophic lateral sclerosis.

PubMed ID
PubMed Central ID
PMC4145400 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neurobiol. Aging
    Title
    Neurobiology of Aging
    Publication Year
    1980-
    ISBN/ISSN
    0197-4580
    Data From Reference
    Alleles (10)
    Genes (5)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (1)
    Transgenic Constructs (9)