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Mosquitoes activate innate immune response signaling pathways upon infection, as a resistance mechanism to fight pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, phenotypic costs ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra\u2010thoracic zymosan injection on <jats:italic>A. aegypti<\/jats:italic> flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin A expression in fat bodies in a time\u2010dependent manner that compromised flight activity. Although oxidant levels in flight muscle were hardly altered, ATP\u2010linked respiratory rates driven by mitochondrial pyruvate+proline oxidation were significantly reduced at 24 h upon zymosan injection. Oxidative phosphorylation coupling was preserved regardless of innate immune response activation along 24 h. Importantly, rotenone\u2010sensitive respiration and complex I\u2010III activity were specifically reduced 24 h upon zymosan injection. Also, loss of complex I activity compromised ATP\u2010linked and maximal respiratory rates mediated by mitochondrial proline oxidation. Finally, the magnitude of innate immune response activation negatively correlated with respiratory rates, regardless of the metabolic states. Collectively, we demonstrate that activation of innate immunity is strongly associated with reduced flight muscle complex I activity with direct consequences to mitochondrial proline oxidation and flight activity. Remarkably, our results indicate a trade\u2010off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism to arbovirus transmission.<\/jats:p>","DOI":"10.1111\/mmi.15269","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T05:25:42Z","timestamp":1715232342000},"page":"683-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Activation of innate immunity selectively compromises mitochondrial complex I, proline oxidation, and flight activity in the major arbovirus vector <i>Aedes aegypti<\/i>"],"prefix":"10.1111","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-2633","authenticated-orcid":false,"given":"Alessandro","family":"Gaviraghi","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Resposta ao Estresse, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Entomologia Molecular (INCT\u2010EM)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-3775","authenticated-orcid":false,"given":"Ana Beatriz F.","family":"Barletta","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Entomologia Molecular (INCT\u2010EM)  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Artr\u00f3podes Hemat\u00f3fagos, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Programa de Biologia Molecular e Biotecnologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-5405","authenticated-orcid":false,"given":"Thiago Luiz Alves E.","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Entomologia Molecular (INCT\u2010EM)  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Artr\u00f3podes Hemat\u00f3fagos, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Programa de Biologia Molecular e Biotecnologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-8799","authenticated-orcid":false,"given":"Matheus P.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Resposta ao Estresse, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Entomologia Molecular (INCT\u2010EM)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-4676","authenticated-orcid":false,"given":"Marcos H. 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