Skip to main content

New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis

Bastow, Emma L, Peswani, Amber Rose, Tarrant, Daniel S J, Pentland, Daniel R, Chen, Xi, Morgan, Alan, Staniforth, Gemma L., Tullet, Jennifer M.A., Rowe, Michelle L., Howard, Mark J., and others. (2016) New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis. Journal of cell science, 129 (21). pp. 4118-4129. ISSN 1477-9137. (doi:10.1242/jcs.190298) (KAR id:58393)

PDF Publisher pdf
Language: English

Download (1MB) Preview
[thumbnail of Bastow et al 2016.pdf]
This file may not be suitable for users of assistive technology.
Request an accessible format
Official URL:


A number of genes have been linked to familial forms of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Over 150 mutations within the gene encoding superoxide dismutase 1 (SOD1) have been implicated in ALS, but why such mutations lead to ALS-associated cellular dysfunction is unclear. In this study, we identify how ALS-linked SOD1 mutations lead to changes in the cellular health of the yeast Saccharomyces cerevisiae We find that it is not the accumulation of aggregates but the loss of Sod1 protein stability that drives cellular dysfunction. The toxic effect of Sod1 instability does not correlate with a loss of mitochondrial function or increased production of reactive oxygen species, but instead prevents acidification of the vacuole, perturbs metabolic regulation and promotes senescence. Central to the toxic gain-of-function seen with the SOD1 mutants examined was an inability to regulate amino acid biosynthesis. We also report that leucine supplementation results in an improvement in motor function in a Caenorhabditis elegans model of ALS. Our data suggest that metabolic dysfunction plays an important role in Sod1-mediated toxicity in both the yeast and worm models of ALS.

Item Type: Article
DOI/Identification number: 10.1242/jcs.190298
Uncontrolled keywords: ALS; Metabolism; SOD1; Vacuole; Yeast
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (
Medical Research Council (
Depositing User: Jennifer Tullet
Date Deposited: 04 Nov 2016 10:34 UTC
Last Modified: 12 Jul 2022 10:41 UTC
Resource URI: (The current URI for this page, for reference purposes)
Tullet, Jennifer M.A.:
Tuite, Mick F.:
Gourlay, Campbell W.:
  • Depositors only (login required):


Downloads per month over past year