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One such effector, RidL, is known to inhibit retrograde trafficking by interacting with the retromer complex via its N-terminal domain. Here, we identify a second function of RidL mediated by its C-terminal domain, which directly binds to the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) and related large GTPases. In vitro, RidL reduces Drp1 GTPase activity and disrupts its oligomerization. During infection, RidL localizes to mitochondria, enhances the accumulation of Drp1 and the outer membrane protein Tom20, and impairs mitochondrial dynamics and function. Moreover, in\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    -infected cells, RidL promotes phosphorylation of Drp1 at Ser616, leading to Drp1 activation and mitochondrial fragmentation. These findings establish RidL as a bifunctional effector that targets both the retromer complex and Drp1 through distinct domains. By interfering with host mitochondrial dynamics, RidL enables\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    to remodel host organelles and optimize conditions for intracellular replication.\n                  <\/jats:p>","DOI":"10.1038\/s44319-026-00823-3","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:50:11Z","timestamp":1780735811000},"page":"3759-3787","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Legionella effector RidL binds the large fission GTPase Drp1 to promote mitochondrial fragmentation"],"prefix":"10.1038","volume":"27","author":[{"given":"Ana","family":"Katic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4466-5299","authenticated-orcid":false,"given":"Elizabeth Teresa","family":"Vittori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0313-7965","authenticated-orcid":false,"given":"Stefanie","family":"Halter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7490-8199","authenticated-orcid":false,"given":"A Leoni","family":"Swart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-9288","authenticated-orcid":false,"given":"Milad","family":"Radiom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-1990","authenticated-orcid":false,"given":"Francisco Javier","family":"Garc\u00eda-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0547-2754","authenticated-orcid":false,"given":"Tobias","family":"J\u00e4ggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8647-7317","authenticated-orcid":false,"given":"Xiaodan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-4872","authenticated-orcid":false,"given":"Jason A","family":"Mears","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-9190","authenticated-orcid":false,"given":"Carmen","family":"Buchrieser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-094X","authenticated-orcid":false,"given":"Pedro","family":"Escoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-7068","authenticated-orcid":false,"given":"Vikram Govind","family":"Panse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-9301","authenticated-orcid":false,"given":"Hubert","family":"Hilbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"823_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15406","volume":"8","author":"K Arasaki","year":"2017","unstructured":"Arasaki K, Mikami Y, Shames SR, Inoue H, Wakana Y, Tagaya M (2017) Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17. 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