{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:00:03Z","timestamp":1793944803896,"version":"4.8.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Mitochondria function not only as metabolic and bioenergetic centers but also as critical signaling hubs that integrate cellular context with innate immune response. The mitochondrial antiviral-signaling protein (MAVS), anchored to the outer mitochondrial membrane, is a central adaptor in the RIG-I-like receptor (RLR) pathway, orchestrating type I interferon (IFN) production and apoptosis. Although long regarded as a docking platform for RLR-derived signals, recent advances, particularly concerning its diverse post-translational modifications (PTMs), reveal MAVS as a dynamic integrator that decodes cellular stress and metabolic cues to fine-tune antiviral immunity. Canonical PTMs such as ubiquitination and phosphorylation highlight the importance of precisely controlling both the initiation and downregulation of MAVS signaling, but recent discoveries substantially broaden this regulatory landscape. Stress-responsive phosphorylation mediated via the ASK1\u2013p38 MAPK pathway enhances MAVS signaling capacity under oxidative and ER stress, linking cellular damage to amplified interferon production. In parallel, a newly identified vitamin K\u2013dependent carboxylation of MAVS reshapes downstream signaling by promoting interferon induction while restraining apoptosis, introducing a regulatory layer that may reflect the metabolic context surrounding GGCX activity, including vitamin K availability. Understanding this multilayered regulatory network not only redefines MAVS as a stress-sensitive mitochondrial signaling hub responsive to cellular context but also highlights new avenues for therapeutic modulation of innate immunity and cell fate during viral infection. This review summarizes emerging insights into PTM-mediated regulation of MAVS and outlines their broader implications for mitochondrial antiviral signaling.<\/jats:p>","DOI":"10.3389\/fphys.2026.1907325","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:10:21Z","timestamp":1787782221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Post-translational control of MAVS signaling: linking mitochondrial antiviral immunity to metabolic and cellular stress contexts"],"prefix":"10.3389","volume":"17","author":[{"given":"Nao","family":"Morimoto","sequence":"first","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University","place":["Sapporo, Japan"]},{"name":"Japan Science and Technology Agency (JST) Fusion Oriented Research for Disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST)","place":["Kawaguchi, Japan"]},{"name":"Suntory SunRiSE Fellow, Suntory Foundation of Life Sciences","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5016","DOI":"10.1038\/s41467-022-32628-y","article-title":"The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation","volume":"13","author":"Bai","year":"2022","journal-title":"Nat. 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