{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:14:24Z","timestamp":1787498064943,"version":"build-2736575974"},"posted":{"date-parts":[[2025,10,23]]},"group-title":"Pharmacology and Toxicology","reference-count":82,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35ES035049"],"award-info":[{"award-number":["R35ES035049"]}],"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":["T32ES021432"],"award-info":[{"award-number":["T32ES021432"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Environmental factors including chemical exposures are important contributors to Parkinson\u2019s disease (PD). Nearly all well-validated chemicals involved in PD affect mitochondria, and the great majority of those identified inhibit mitochondrial complex I, causing ATP depletion and oxidative stress. We hypothesized that inhibition of mitochondrial complex III would also cause dopaminergic neurotoxicity. Using\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  to evaluate the\n                  <jats:italic>in vivo<\/jats:italic>\n                  effects of complex III-inhibiting pesticides antimycin A and pyraclostrobin, we found that both caused selective dopaminergic neurotoxicity. We evaluated exacerbation of dopaminergic neurotoxicity by the presence of \u03b1-synuclein, and\n                  <jats:italic>pdr-1<\/jats:italic>\n                  \/PRKN and\n                  <jats:italic>pink-1<\/jats:italic>\n                  \/PINK1 mutant backgrounds and found increased neurotoxicity for\n                  <jats:italic>pdr-1<\/jats:italic>\n                  . Complex III inhibition caused a more-oxidized cellular environment in those neurons and pharmacological and genetic antioxidant interventions rescued neurotoxicity, but energetic rescue attempts did not. Finally, optogenetic production of superoxide anion specifically at complex III caused dopaminergic neuronal damage. Thus, redox stress at complex III following chemical exposure causes dopaminergic neurotoxicity\n                  <jats:italic>in vivo<\/jats:italic>\n                  in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2025.10.21.683798","type":"posted-content","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T18:35:30Z","timestamp":1761244530000},"source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of mitochondrial complex III causes selective dopaminergic neurotoxicity by redox stress in\n                  <i>Caenorhabditis elegans<\/i>"],"prefix":"10.64898","author":[{"given":"Javier","family":"Huayta","sequence":"first","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliyah S.","family":"Webster","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Jhaver","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1219-0983","authenticated-orcid":false,"given":"Joel N.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University, Durham NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026073006100492000_2025.10.21.683798v2.1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-095610"},{"key":"2026073006100492000_2025.10.21.683798v2.2","doi-asserted-by":"publisher","DOI":"10.1136\/BMJ-2024-080952"},{"key":"2026073006100492000_2025.10.21.683798v2.3","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-230357"},{"key":"2026073006100492000_2025.10.21.683798v2.4","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-181493"},{"key":"2026073006100492000_2025.10.21.683798v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.197"},{"key":"2026073006100492000_2025.10.21.683798v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70327-7"},{"key":"2026073006100492000_2025.10.21.683798v2.7","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2017.00177"},{"key":"2026073006100492000_2025.10.21.683798v2.8","doi-asserted-by":"publisher","DOI":"10.1186\/S12859-021-04285-3"},{"key":"2026073006100492000_2025.10.21.683798v2.9","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.192138"},{"key":"2026073006100492000_2025.10.21.683798v2.10","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.360279"},{"key":"2026073006100492000_2025.10.21.683798v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-020-00107-x"},{"key":"2026073006100492000_2025.10.21.683798v2.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103538"},{"key":"2026073006100492000_2025.10.21.683798v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04059-0"},{"key":"2026073006100492000_2025.10.21.683798v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.crtox.2022.100084"},{"key":"2026073006100492000_2025.10.21.683798v2.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02970-5"},{"key":"2026073006100492000_2025.10.21.683798v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2017.07.019"},{"key":"2026073006100492000_2025.10.21.683798v2.17","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2014.933722"},{"key":"2026073006100492000_2025.10.21.683798v2.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-34-10756.2003"},{"key":"2026073006100492000_2025.10.21.683798v2.19","doi-asserted-by":"publisher","DOI":"10.1177\/0960327110392084"},{"key":"2026073006100492000_2025.10.21.683798v2.20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.840272"},{"key":"2026073006100492000_2025.10.21.683798v2.21","doi-asserted-by":"publisher","DOI":"10.14573\/altex.2501151"},{"key":"2026073006100492000_2025.10.21.683798v2.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2011.08.009"},{"key":"2026073006100492000_2025.10.21.683798v2.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2017.11.010"},{"key":"2026073006100492000_2025.10.21.683798v2.24","unstructured":"Inc. 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