{"doi":"10.1242/jcs.248880","title":"Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton","abstract":"ABSTRACT 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–ER interaction, heightened intracellular Ca2+ levels and elevated Rac activation after chemokine stimulation. Restoring a mitochondria–ER 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–ER interaction to suppress Rac activation, and uncovered a previously unrecognized role of MFN2 in regulating cell migration and the actin cytoskeleton. This article has an associated First Person interview with the first authors of the paper.","journal":"Journal of Cell Science","year":2020,"id":97959,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":484215,"name":"Alan Y. Hsu","orcid":"0000-0001-5680-345X","position":1,"is_corresponding":false},{"id":484216,"name":"Yueyang Wang","orcid":"0000-0002-5445-8186","position":2,"is_corresponding":false},{"id":485449,"name":"Ramizah Syahirah","orcid":null,"position":3,"is_corresponding":false},{"id":484217,"name":"Tianqi Wang","orcid":"0000-0003-4989-049X","position":4,"is_corresponding":false},{"id":484218,"name":"Jacob Jeffries","orcid":"0000-0003-2704-9675","position":5,"is_corresponding":false},{"id":481181,"name":"Xu Wang","orcid":"0000-0001-7327-4537","position":6,"is_corresponding":false},{"id":484219,"name":"Haroon Mohammad","orcid":"0000-0002-8843-8933","position":7,"is_corresponding":false},{"id":106917,"name":"Mohamed N. Seleem","orcid":"0000-0003-0939-0458","position":8,"is_corresponding":false},{"id":447261,"name":"David M. Umulis","orcid":"0000-0003-1913-2284","position":9,"is_corresponding":false},{"id":484220,"name":"Qing Deng","orcid":"0000-0002-9254-9951","position":10,"is_corresponding":false},{"id":301468,"name":"Wenqing Zhou","orcid":"0000-0002-8800-3745","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T22:36:34.157932Z","pmid":"32788232","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}