{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:04:59Z","timestamp":1789733099748,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,14]]},"group-title":"Immunology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R35GM142689"],"award-info":[{"award-number":["R35GM142689"]}]},{"name":"NIH","award":["1R35GM162011"],"award-info":[{"award-number":["1R35GM162011"]}]},{"name":"NIH","award":["T32AI007520"],"award-info":[{"award-number":["T32AI007520"]}]},{"name":"NIH","award":["2T32AI005284-41A1"],"award-info":[{"award-number":["2T32AI005284-41A1"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["RR170047"],"award-info":[{"award-number":["RR170047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Dysregulated immunity, a hallmark of many human diseases, co-occurs with mitochondrial dysfunction and is commonly associated with misprimed primary immune signaling. While transcriptionally well-characterized, the impact of mitochondria on the host response at the protein level is less clear. Using\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  approaches including proteotranscriptomics, our data suggest that OXPHOS promotes expression of early, cell autonomous immune proteins whereas mitochondrial perturbation favors mediators of cell extrinsic responses like inflammation. This response is independent of immune cues, time-dependent, conserved, and occurs across tissues in mouse models of mitochondrial dysfunction. These data illustrate unappreciated roles for mitochondrial state in adapting host responses at the protein level, which have implications for complex disease etiology and the ancestral origins for eukaryotic immune sensing.\n                <\/jats:p>","DOI":"10.64898\/2026.09.07.749965","type":"posted-content","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:15:25Z","timestamp":1789406125000},"source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial perturbation adapts the proteome from early to advanced immune responses"],"prefix":"10.64898","author":[{"given":"Jessica","family":"Alvarez","sequence":"first","affiliation":[{"name":"Molecular Microbiology Ph.D. program, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Rivera","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Ph.D. program, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarahbeth","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyron","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Kanth Chitta","sequence":"additional","affiliation":[{"name":"Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lemoff","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-2545","authenticated-orcid":false,"given":"Dustin C.","family":"Hancks","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center; Dallas, 75235, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091804351624000_2026.09.07.749965v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06866-z"},{"key":"2026091804351624000_2026.09.07.749965v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0675-0"},{"key":"2026091804351624000_2026.09.07.749965v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.66"},{"key":"2026091804351624000_2026.09.07.749965v1.4","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s42255-023-00783-1","article-title":"Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction","volume":"5","year":"2023","journal-title":"Nat. Metab"},{"key":"2026091804351624000_2026.09.07.749965v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/0022-5193(67)90079-3"},{"key":"2026091804351624000_2026.09.07.749965v1.6","first-page":"e02096","article-title":"Mitochondria and Viral Infection: Advances and Emerging Battlefronts","volume":"13","year":"2022","journal-title":"Mbio"},{"key":"2026091804351624000_2026.09.07.749965v1.7","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41577-021-00529-8","article-title":"A guide to interrogating immunometabolism","volume":"21","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2026091804351624000_2026.09.07.749965v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.012"},{"key":"2026091804351624000_2026.09.07.749965v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80085-9"},{"key":"2026091804351624000_2026.09.07.749965v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature14156"},{"key":"2026091804351624000_2026.09.07.749965v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature25986"},{"key":"2026091804351624000_2026.09.07.749965v1.12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41577-025-01132-x","article-title":"Trained immunity in chronic inflammatory diseases and cancer","volume":"25","year":"2025","journal-title":"Nat. Rev. Immunol"},{"key":"2026091804351624000_2026.09.07.749965v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.004"},{"key":"2026091804351624000_2026.09.07.749965v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.06.006"},{"key":"2026091804351624000_2026.09.07.749965v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"2026091804351624000_2026.09.07.749965v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3535"},{"key":"2026091804351624000_2026.09.07.749965v1.17","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00665-20"},{"key":"2026091804351624000_2026.09.07.749965v1.18","doi-asserted-by":"crossref","first-page":"e0250125","DOI":"10.1128\/mbio.02501-25","article-title":"mGem: More than building blocks? Mitochondrial metabolism, viruses, and the host response to infection","volume":"17","year":"2026","journal-title":"mBio"},{"key":"2026091804351624000_2026.09.07.749965v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/nature19754"},{"key":"2026091804351624000_2026.09.07.749965v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.08.017"},{"key":"2026091804351624000_2026.09.07.749965v1.21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012673"},{"key":"2026091804351624000_2026.09.07.749965v1.22","doi-asserted-by":"crossref","first-page":"e3001045","DOI":"10.1371\/journal.pbio.3001045","article-title":"Signatures of host\u2013pathogen evolutionary conflict reveal MISTR\u2014A conserved MItochondrial STress Response network","volume":"18","year":"2020","journal-title":"Plos Biol"},{"key":"2026091804351624000_2026.09.07.749965v1.23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25687"},{"key":"2026091804351624000_2026.09.07.749965v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.06.044"},{"key":"2026091804351624000_2026.09.07.749965v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2021.10.006)"},{"key":"2026091804351624000_2026.09.07.749965v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03927-z"},{"key":"2026091804351624000_2026.09.07.749965v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nature15400"},{"key":"2026091804351624000_2026.09.07.749965v1.28","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1016\/j.cell.2023.06.005","article-title":"TMEM106B is a receptor mediating ACE2-independent SARS-CoV-2 cell entry","volume":"186","year":"2023","journal-title":"Cell"},{"key":"2026091804351624000_2026.09.07.749965v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.10.002"},{"key":"2026091804351624000_2026.09.07.749965v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.057"},{"key":"2026091804351624000_2026.09.07.749965v1.31","first-page":"105","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy","volume":"509","year":"2013","journal-title":"Nature"},{"key":"2026091804351624000_2026.09.07.749965v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601823"},{"key":"2026091804351624000_2026.09.07.749965v1.33","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1761653"},{"key":"2026091804351624000_2026.09.07.749965v1.34","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00775-10"},{"key":"2026091804351624000_2026.09.07.749965v1.35","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1220"},{"key":"2026091804351624000_2026.09.07.749965v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05851-w"},{"key":"2026091804351624000_2026.09.07.749965v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06409-6"},{"key":"2026091804351624000_2026.09.07.749965v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.10.008"},{"key":"2026091804351624000_2026.09.07.749965v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/nature06905"},{"key":"2026091804351624000_2026.09.07.749965v1.40","doi-asserted-by":"crossref","unstructured":"B. Shrum , R. V. Anantha , S. X. Xu , M. Donnelly , S. M. Haeryfar , J. K. McCormick , T. Mele , A robust scoring system to evaluate sepsis severity in an animal model. BMC Res. Notes 7, 233 (2014).","DOI":"10.1186\/1756-0500-7-233"},{"key":"2026091804351624000_2026.09.07.749965v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.02.004"},{"key":"2026091804351624000_2026.09.07.749965v1.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006214107"},{"key":"2026091804351624000_2026.09.07.749965v1.43","doi-asserted-by":"publisher","DOI":"10.1084\/JEM.20221839"},{"key":"2026091804351624000_2026.09.07.749965v1.44","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000051367.92927.07"},{"key":"2026091804351624000_2026.09.07.749965v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3700"},{"key":"2026091804351624000_2026.09.07.749965v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3433"},{"key":"2026091804351624000_2026.09.07.749965v1.47","doi-asserted-by":"crossref","first-page":"15983","DOI":"10.3390\/ijms232415983","article-title":"The Mammalian Cysteine Protease Legumain in Health and Disease","volume":"23","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026091804351624000_2026.09.07.749965v1.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811892115"},{"key":"2026091804351624000_2026.09.07.749965v1.49","doi-asserted-by":"publisher","DOI":"10.1172\/JCI160766"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.07.749965","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:35:25Z","timestamp":1789731325000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.07.749965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":49,"URL":"https:\/\/doi.org\/10.64898\/2026.09.07.749965","relation":{},"subject":[],"published":{"date-parts":[[2026,9,14]]},"subtype":"preprint"}}