{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:49:26Z","timestamp":1792565366295,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mitochondria are central regulators of retinal bioenergetics and innate immune signaling, yet how mitochondrial genetic background and aging jointly influence immunometabolic responses in the retina remains poorly defined. Here, we investigated the effects of mitochondrial DNA (mtDNA) variation on retinal function and the combined effects of mtDNA variation and age on bioenergetic composition, mtDNA damage, and the microglial expression and intracellular localization of stimulator of interferon genes (STING) protein. Using mitochondrial\u2013nuclear eXchange (MNX) mice harboring identical C57BL\/6J nuclear genomes but distinct C57 or C3H mtDNA haplotypes, we assessed oxidative phosphorylation complex composition, electrophysiological function, mtDNA damage, and microglial STING dynamics across the lifespan and following acute intraocular pressure (IOP) elevation. Aging was associated with increased mtDNA damage and remodeling of oxidative phosphorylation complex composition, characterized by reduced Complex III and V abundance and increased Complex IV. Despite these age\u2010associated changes, photoreceptor\u2010 and retinal ganglion cell\u2010associated retinal responses were preserved at early ages, whereas bipolar cell\u2010associated responses differed by mtDNA background. Microglial STING expression increased with age. Acute IOP elevation was associated with differential microglial STING dynamics and STING association with lysosomal compartments decreased with age. Together, these findings demonstrate that mitochondrial genetic background and aging influence retinal bioenergetics and neuroimmune protein expression and identify mtDNA variation as a modifier of age\u2010associated microglial STING expression in the retina.<\/jats:p>","DOI":"10.1111\/acel.70771","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:10:58Z","timestamp":1792062658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Genetic Background Shapes Baseline Retinal Function, Age\u2010Related Bioenergetic Remodeling, and Microglial\n                    <scp>STING<\/scp>\n                    Phenotypes"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-1924","authenticated-orcid":false,"given":"McKenna M.","family":"Somerville","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney S.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Ballinger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1857-6633","authenticated-orcid":false,"given":"Alecia K.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1998.0661"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology14091140"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010025\u201001390\u2010y"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20131433"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1153934"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2005.11.007"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91141"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13\u201012415"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.07.025"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2011.02.006"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.03.006"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.70013"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305462110"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.02.019"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103867"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.11.3324"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20130029"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010018\u20100059\u20104"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11040325"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006373\u20101"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2012.03.004"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.88.1.98"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00220.2019"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1976"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2025.5559"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.99.2.177"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073689"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2409493121"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.571479"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010019\u201001665\u2010y"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1125115"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010181184"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1429005"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.10.008"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15070479"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2024.1293"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci17741"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.03.003"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-025-10199-x"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14778"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925\u20104439(95)00021\u2010U"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.77.6.667"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S9078"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.514"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2019.4188"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70771","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70771","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:35:52Z","timestamp":1792564552000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/acel.70771"],"URL":"https:\/\/doi.org\/10.1111\/acel.70771","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70771"}}