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While various pathogens have developed strategies to manipulate mitochondrial dynamics, the mechanisms underlying bacterial infection and mitochondrial dynamics interactions remain poorly understood. Here, we demonstrate that B. abortus induces mitochondrial fragmentation via IRE1\u03b1. Our findings reveal that Brucella-induced mitochondrial fission is mediated by dynamin-related protein 1 (DRP1), a pivotal regulator of mitochondrial fission. Moreover, we have demonstrated that DRP1 is activated by the UPR. Brucella-induced fragmentation leads to mitochondrial energetic dysfunction, marked by impaired mitochondrial ATP production and compromised bioenergetic capacity. Furthermore, we reveal a novel role for DRP1 in regulating type I IFN production and signaling during B. abortus infection. Mechanistically, mitochondrial fission facilitates the release of mitochondrial DNA, a potent inducer of type I IFN responses. Despite its impact on mitochondrial function and IFN signaling, DRP1 does not influence the control of B. abortus infection. Our findings uncover a unique mechanism by which B. abortus\u2013induced UPR triggers mitochondrial fragmentation affecting innate immune signaling and cellular metabolism.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf198","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T19:47:33Z","timestamp":1755200853000},"page":"2688-2699","source":"Crossref","is-referenced-by-count":2,"title":["<i>Brucella abortus<\/i>\n                    induces dynamin-related protein 1 (DRP1)\u2013dependent mitochondrial fission in infected macrophages via stress sensor IRE1\u03b1 altering metabolic function"],"prefix":"10.1093","volume":"214","author":[{"given":"Erika S","family":"Guimar\u00e3es","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte,","place":["Brazil"]},{"name":"Departamento de Gen\u00e9tica, Ecologia e Evolu\u00e7\u00e3o, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco T\u00falio R","family":"Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro M","family":"Moraes-Vieira","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Evolu\u00e7\u00e3o, Microbiologia e Imunologia, Universidade Estadual de Campinas , Campinas, S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4062-5577","authenticated-orcid":false,"given":"Sergio C","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte,","place":["Brazil"]},{"name":"Institut Pasteur de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]},{"name":"Departamento de Imunologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"2026081320014536000_vkaf198-B1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature12985","article-title":"Mitochondrial form and function","volume":"505","author":"Friedman","year":"2014","journal-title":"Nature"},{"key":"2026081320014536000_vkaf198-B2","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nrm2275","article-title":"Functions and dysfunctions of mitochondrial dynamics","volume":"8","author":"Detmer","year":"2007","journal-title":"Nat Rev Mol Cell 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