{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:35:52Z","timestamp":1790069752254,"version":"4.0.1"},"reference-count":53,"publisher":"The Company of Biologists","issue":"17","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":163,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM119787"],"award-info":[{"award-number":["R35GM119787"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD073156"],"award-info":[{"award-number":["R01HD073156"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA023168"],"award-info":[{"award-number":["P30CA023168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neutrophils rely on glycolysis for energy production. How mitochondria regulate neutrophil function is not fully understood. Here, we report that mitochondrial outer membrane protein Mitofusin 2 (MFN2) regulates neutrophil homeostasis and chemotaxis in vivo. Mfn2-deficient neutrophils are released from the hematopoietic tissue, trapped in the vasculature in zebrafish embryos, and not capable of chemotaxis. Consistent with this, human neutrophil-like cells that are deficient for MFN2 fail to arrest on activated endothelium under sheer stress or perform chemotaxis on 2D surfaces. Deletion of MFN2 results in a significant reduction of neutrophil infiltration to the inflamed peritoneal cavity in mice. Mechanistically, MFN2-deficient neutrophil-like cells display disrupted mitochondria\u2013ER interaction, heightened intracellular Ca2+ levels and elevated Rac activation after chemokine stimulation. Restoring a mitochondria\u2013ER tether rescues the abnormal Ca2+ levels, Rac hyperactivation and chemotaxis defect resulting from MFN2 depletion. Finally, inhibition of Rac activation restores chemotaxis in MFN2-deficient neutrophils. Taken together, we have identified that MFN2 regulates neutrophil migration via maintaining the mitochondria\u2013ER interaction to suppress Rac activation, and uncovered a previously unrecognized role of MFN2 in regulating cell migration and the actin cytoskeleton.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first authors of the paper.<\/jats:p>","DOI":"10.1242\/jcs.248880","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T16:01:51Z","timestamp":1597161711000},"source":"Crossref","is-referenced-by-count":29,"title":["Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton"],"prefix":"10.1242","volume":"133","author":[{"given":"Wenqing","family":"Zhou","sequence":"first","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5680-345X","authenticated-orcid":false,"given":"Alan Y.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-8186","authenticated-orcid":false,"given":"Yueyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramizah","family":"Syahirah","sequence":"additional","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Jeffries","sequence":"additional","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Purdue University 2 Department of Agricultural & Biological Engineering , , West Lafayette, IN 47907 , USA"},{"name":"Weldon School of Biomedical Engineering, Purdue University 3 , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haroon","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Purdue University 4 Department of Comparative Pathobiology , , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[{"name":"Purdue University 4 Department of Comparative Pathobiology , , West Lafayette, IN 47907 , USA"},{"name":"Purdue Institute for Inflammation, Immunology & Infectious Disease, Purdue University 5 , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Umulis","sequence":"additional","affiliation":[{"name":"Purdue University 2 Department of Agricultural & Biological Engineering , , West Lafayette, IN 47907 , USA"},{"name":"Weldon School of Biomedical Engineering, Purdue University 3 , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-9951","authenticated-orcid":false,"given":"Qing","family":"Deng","sequence":"additional","affiliation":[{"name":"Purdue University 1 Department of Biological Sciences , , West Lafayette, IN 47907 , USA"},{"name":"Purdue Institute for Inflammation, Immunology & Infectious Disease, Purdue University 5 , West Lafayette, IN 47907 , USA"},{"name":"Purdue University Center for Cancer Research, Purdue University 6 , West Lafayette, IN 47907 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"2024061318590618300_JCS248880C1","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.immuni.2013.02.018","article-title":"Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice","volume":"38","author":"Abram","year":"2013","journal-title":"Immunity"},{"key":"2024061318590618300_JCS248880C2","doi-asserted-by":"publisher","first-page":"2958","DOI":"10.1038\/s41467-018-05387-y","article-title":"Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production","volume":"9","author":"Amini","year":"2018","journal-title":"Nat. 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