{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T17:42:31Z","timestamp":1769881351198,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009771","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000}}],"reference-count":107,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Multiple Mitochondrial Dysfunctions Syndrome 1 (MMDS1) is a rare, autosomal recessive disorder caused by mutations in the<jats:italic>NFU1<\/jats:italic>gene. NFU1 is responsible for delivery of iron-sulfur clusters (ISCs) to recipient proteins which require these metallic cofactors for their function. Pathogenic variants of<jats:italic>NFU1<\/jats:italic>lead to dysfunction of its target proteins within mitochondria. To date, 20<jats:italic>NFU1<\/jats:italic>variants have been reported and the unique contributions of each variant to MMDS1 pathogenesis is unknown. Given that over half of MMDS1 individuals are compound heterozygous for different<jats:italic>NFU1<\/jats:italic>variants, it is valuable to investigate individual variants in an isogenic background. In order to understand the shared and unique phenotypes of<jats:italic>NFU1<\/jats:italic>variants, we used CRISPR\/Cas9 gene editing to recreate exact patient variants of<jats:italic>NFU1<\/jats:italic>in the orthologous gene,<jats:italic>nfu-1<\/jats:italic>(formerly<jats:italic>lpd-8)<\/jats:italic>, in<jats:italic>C<\/jats:italic>.<jats:italic>elegans<\/jats:italic>. Five mutant<jats:italic>C<\/jats:italic>.<jats:italic>elegans<\/jats:italic>alleles focused on the presumptive iron-sulfur cluster interaction domain were generated and analyzed for mitochondrial phenotypes including respiratory dysfunction and oxidative stress. Phenotypes were variable between the mutant<jats:italic>nfu-1<\/jats:italic>alleles and generally presented as an allelic series indicating that not all variants have lost complete function. Furthermore, reactive iron within mitochondria was evident in some, but not all,<jats:italic>nfu-1<\/jats:italic>mutants indicating that iron dyshomeostasis may contribute to disease pathogenesis in some MMDS1 individuals.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009771","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T17:39:58Z","timestamp":1630085998000},"page":"e1009771","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Allele-specific mitochondrial stress induced by Multiple Mitochondrial Dysfunctions Syndrome 1 pathogenic mutations modeled in Caenorhabditis elegans"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-6123","authenticated-orcid":true,"given":"Peter 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