{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:09:25Z","timestamp":1784308165714,"version":"3.55.0"},"reference-count":92,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS100547"],"award-info":[{"award-number":["R01NS100547"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS106951"],"award-info":[{"award-number":["R01NS106951"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS113559"],"award-info":[{"award-number":["R01NS113559"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Neuromuscular dysfunction is a common feature of mitochondrial diseases and frequently presents as ataxia, spasticity and\/or dystonia, all of which can severely impact individuals with mitochondrial diseases. Dystonia is one of the most common symptoms of multiple mitochondrial dysfunctions syndrome 1 (MMDS1), a disease associated with mutations in the causative gene (NFU1) that impair iron\u2013sulfur cluster biogenesis. We have generated Caenorhabditis elegans strains that recreated patient-specific point variants in the C. elegans ortholog (nfu-1) that result in allele-specific dysfunction. Each of these mutants, Gly147Arg and Gly166Cys, have altered acetylcholine signaling at neuromuscular junctions, but opposite effects on activity and motility. We found that the Gly147Arg variant was hypersensitive to acetylcholine and that knockdown of acetylcholine release rescued nearly all neuromuscular phenotypes of this variant. In contrast, we found that the Gly166Cys variant caused predominantly postsynaptic acetylcholine hypersensitivity due to an unclear mechanism. These results are important for understanding the neuromuscular conditions of MMDS1 patients and potential avenues for therapeutic intervention.<\/jats:p>","DOI":"10.1242\/dmm.049594","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T11:14:18Z","timestamp":1673867658000},"source":"Crossref","is-referenced-by-count":1,"title":["Patient-specific variants of NFU1\/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-6123","authenticated-orcid":false,"given":"Peter A.","family":"Kropp","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 Laboratory of Biochemistry and Genetics , , Bethesda, MD 20892 , USA"},{"name":"Biology Department, Kenyon College 2 , Gambier, OH 43022 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Rogers","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 Laboratory of Biochemistry and Genetics , , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney E.","family":"Kelly","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 Laboratory of Biochemistry and Genetics , , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"McWhirter","sequence":"additional","affiliation":[{"name":"Vanderbilt University 3 Department of Cell and Developmental Biology , , Nashville, TN 37235 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willow D.","family":"Goff","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 Laboratory of Biochemistry and Genetics , , Bethesda, MD 20892 , USA"},{"name":"Colgate University 4 Biology Department , , Hamilton, NY 13346 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Levitan","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 Laboratory of Biochemistry and Genetics , , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"David M.","family":"Miller","sequence":"additional","affiliation":[{"name":"Vanderbilt University 3 Department of Cell and Developmental Biology , , Nashville, TN 37235 , USA"},{"name":"Vanderbilt University 5 Neuroscience Graduate Program , , Nashville, TN 37235 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Golden","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 Laboratory of Biochemistry and Genetics , , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"2023020113081974200_DMM049594C1","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.2147\/DDDT.S191240","article-title":"Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation","volume":"13","author":"Abdel-Wahab","year":"2019","journal-title":"Drug. 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