{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:39:54Z","timestamp":1793378394570,"version":"4.5.0"},"reference-count":30,"publisher":"American Society for Cell Biology (ASCB)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>Patient mutations within Drp1, the master regulator of mitochondrial fission, lead to severe neurological defects and poor patient outcomes. Many of these mutations have been characterized as causing functional or assembly defects in Drp1, but our study highlights three mutations (G362S, E379K, and E410K) that do not have an apparent defect in core Drp1 functions. We investigated the possibility that these mutations impact interactions with Mff, a pro-fission partner protein of Drp1. Negative stain electron microscopy and mass photometry were used to visualize and quantify assembly properties, while GTPase assays assessed the enzymatic activities of distinct proteins and protein complexes. In parallel, confocal microscopy highlighted the effects of overexpressing each mutation on mitochondrial morphology in cells. We discovered that G362S and E410K Drp1 mutations limit interactions with Mff, as co-assembly into larger filaments and the associated stimulation of GTPase activity was inhibited. Conversely, the E379K mutation is able to form functional complexes with Mff, and no apparent defect was observed, warranting additional studies focused on unique mitochondrial fission attributes. Overall, our data highlight the complex nature of disease-associated mutations in Drp1 and emphasize the importance of Drp1-Mff interactions in sustaining mitochondrial and cellular health.<\/jats:p>","DOI":"10.1091\/mbc.e25-01-0022","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T19:17:53Z","timestamp":1785957473000},"source":"Crossref","is-referenced-by-count":0,"title":["The identification of Drp1 patient mutations that limit interactions with Mff"],"prefix":"10.1091","volume":"37","author":[{"given":"Yuli","family":"Buckley","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anelise N.","family":"Hutson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna L.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaiah M.","family":"Waiters","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayanlee De Le\u00f3n","family":"Cordero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S. K.","family":"Stoll","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Mears","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH, 44016"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad029"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02290-z"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.142430"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw059"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.003"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201507035"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01547-9"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0676-6_4"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.680025"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.74"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0211-2"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(05)04043-7"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21-04-0224"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29001-9"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202101284"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201007152"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.54"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260370"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45524-4"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/19024"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37624"},{"key":"e_1_3_4_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.342105"},{"key":"e_1_3_4_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61371"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23729"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903065"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.043"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2023.02.002"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00853-x"},{"key":"e_1_3_4_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12805"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404105200"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:58:09Z","timestamp":1793375889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.E25-01-0022"}},"subtitle":[],"editor":[{"given":"Laura","family":"Lackner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1091\/mbc.E25-01-0022"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e25-01-0022","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"ar90"}}