title: Cell culture models to investigate the selective vulnerability of motoneuronal mitochondria to familial ALS-linked G93ASOD1.
abstract: Mitochondrial damage induced by superoxide dismutase (SOD1) mutants has been proposed to have a causative role in the selective degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). In order to investigate the basis of the tissue specificity of mutant SOD1 we compared the effect of the continuous expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal Madin-Darby Canine Kidney (MDCK) cell lines. Morphological alterations of mitochondria were observed in NSC-34 expressing the G93A mutant (NSC-G93A) but not the wild-type SOD1, whereas a ten-fold greater level of total expression of the mutant had no effect on mitochondria of non-motoneuronal cell lines. Fragmented network, swelling and cristae remodelling but not vacuolization of mitochondria or other intracellular organelles were observed only in NSC-G93A cells. The mitochondrial alterations were not explained by a preferential localization of the mutant within NSC-G93A mitochondria, as a higher amount of the mutant SOD1 was found in mitochondria of MDCK-G93A cells. Our results suggest that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in NSC-34 cells, and that peculiar features in network dynamics may account for the selective alterations of motoneuronal mitochondria.
authors.affiliation: Department of Pharmacology, School of Medicine, Center of Excellence on Neurodegenerative Diseases, University of Milano, Consiglio Nazionale delle Ricerche, CNR, Institute of Neuroscience, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raimondi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangolini
authors.forename: Milena
authors.initials: M
authors.lastname: Rizzardini
authors.forename: Silvia
authors.initials: S
authors.lastname: Tartari
authors.forename: Silvia
authors.initials: S
authors.lastname: Massari
authors.forename: Caterina
authors.initials: C
authors.lastname: Bendotti
authors.forename: Maura
authors.initials: M
authors.lastname: Francolini
authors.forename: Nica
authors.initials: N
authors.lastname: Borgese
authors.forename: Lavinia
authors.initials: L
authors.lastname: Cantoni
authors.forename: Grazia
authors.initials: G
authors.lastname: Pietrini
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000235:genetics; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000473:pathology; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1