{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:03:44Z","timestamp":1791266624595,"version":"4.1.0"},"reference-count":51,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T00:00:00Z","timestamp":1599350400000},"content-version":"vor","delay-in-days":1405,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/J000191\/1"],"award-info":[{"award-number":["BB\/J000191\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["78573"],"award-info":[{"award-number":["78573"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001316","name":"University of Kent","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>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\u2008elegans 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.<\/jats:p>","DOI":"10.1242\/jcs.190298","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T02:09:35Z","timestamp":1474510175000},"page":"4118-4129","source":"Crossref","is-referenced-by-count":54,"title":["New links between <i>SOD1<\/i> and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis"],"prefix":"10.1242","volume":"129","author":[{"given":"Emma L.","family":"Bastow","sequence":"first","affiliation":[{"name":"School of Biosciences, University of Kent 1 Kent Fungal Group , , Canterbury, Kent CT2 7NJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber R.","family":"Peswani","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Kent 1 Kent Fungal Group , , Canterbury, Kent CT2 7NJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S. 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