title: Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an adult onset characterized by loss of both upper and lower motor neurons. In ~10% of cases, patients developed ALS with an apparent genetic linkage (familial ALS or fALS). Approximately 20% of fALS displays mutations in the SOD1 gene encoding superoxide dismutase 1. There are many proposed cellular and molecular mechanisms among which, mitochondrial dysfunctions occur early, prior to symptoms occurrence. In this review, we modeled the effect of mutant SOD1 protein via the formation of a toxic complex with Bcl2 on mitochondrial bioenergetics. Furthermore, we discuss that the shutdown of ATP permeation through mitochondrial outer membrane could lead to both respiration inhibition and temporary mitochondrial hyperpolarization. Moreover, we reviewed mitochondrial calcium signaling, oxidative stress, fission and fusion, autophagy and apoptosis in mutant SOD1-linked ALS. Functional defects in mitochondria appear early before symptoms are manifested in ALS. Therefore, mitochondrial dysfunction is a promising therapeutic target in ALS.
authors.affiliation: Frances and Joseph Weinberg Unit for ALS Research, Farber Institute for the Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Tan
authors.affiliation: Frances and Joseph Weinberg Unit for ALS Research, Farber Institute for the Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Piera
authors.initials: P
authors.lastname: Pasinelli
authors.affiliation: Frances and Joseph Weinberg Unit for ALS Research, Farber Institute for the Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: davide.trotti@jefferson.edu.
authors.forename: Davide
authors.initials: D
authors.lastname: Trotti
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Mitochondria; Oxidative stress