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Recent work illustrates how type I IFNs contribute to the resolution of inflammatory conditions. This involves macrophage-mediated efferocytosis for the clearance of apoptotic cells and the intrinsic capacity of type I IFNs to restrict their own autocrine signaling loops via the IFN-stimulated gene 15 (ISG15) protein. We discuss how this may affect tumor cells and how acetylation-dependent processes can affect the phosphorylation-dependent signaling cascades that augment IFN-dependent gene expression.<\/jats:p>","DOI":"10.37349\/etat.2026.1002399","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:49:51Z","timestamp":1787125791000},"update-policy":"https:\/\/doi.org\/10.37349\/open_exploration_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial checkpoint for interferon responses in macrophages"],"prefix":"10.37349","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-0708","authenticated-orcid":false,"given":"Andreas O.","family":"Mieland","sequence":"first","affiliation":[{"name":"Institute of Toxicology, University Medical Center of Johannes Gutenberg University,  55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-045X","authenticated-orcid":false,"given":"Oliver H.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, University Medical Center of Johannes Gutenberg University,  55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"21850","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.cmet.2017.06.001","article-title":"Specific and Complex Reprogramming of Cellular Metabolism in Myeloid Cells during Innate Immune Responses","volume":"26","author":"Stienstra","year":"2017","journal-title":"Cell Metab"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3390\/ddc5010017","article-title":"Cancer Metabolism and Its Historical & Molecular Foundations: An Overview","volume":"5","author":"Al-Horani","year":"2026","journal-title":"Drugs Drug Candidates"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.immuni.2025.12.010","article-title":"A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages","volume":"59","author":"Dunphy","year":"2026","journal-title":"Immunity"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-012165","article-title":"New insights into the role of IFN-\u03b1\/\u03b2 and TLR7\/8\/9 in cancer immunotherapy and systemic autoimmunity","volume":"13","author":"Krieg","year":"2025","journal-title":"J ImmunoTher Cancer"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.cytogfr.2025.12.008","article-title":"Interferons as therapeutic orchestrators of cancer stem cell plasticity and therapy response","volume":"87","author":"Kasat","year":"2026","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"699","DOI":"10.37349\/etat.2023.00162","article-title":"Protein ISGylation: a posttranslational modification with implications for malignant neoplasms","volume":"4","author":"Tecalco-Cruz","year":"2023","journal-title":"Explor Target Antitumor Ther"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1775143","article-title":"When ISG15 is involved in inflammation","volume":"17","author":"Feng","year":"2026","journal-title":"Front Immunol"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28031337","article-title":"The Functional Roles of ISG15\/ISGylation in Cancer","volume":"28","author":"Yuan","year":"2023","journal-title":"Molecules"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"ISG15 orchestrates dynamic crosstalk between mitochondrial fat oxidation and type 1 interferon in myeloid cells. bioRxiv 2026.01.19.700051 [Preprint]. 2026 [cited 2026 Mar 19]. 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