{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T14:34:59Z","timestamp":1793975699181,"version":"4.8.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR069876"],"award-info":[{"award-number":["AR069876"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["CA216101"],"award-info":[{"award-number":["CA216101"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Metab"],"DOI":"10.1038\/s42255-019-0150-8","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T12:02:28Z","timestamp":1575892948000},"page":"1209-1218","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["Mitochondrial DNA stress signalling protects the nuclear genome"],"prefix":"10.1038","volume":"1","author":[{"given":"Zheng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9695-8771","authenticated-orcid":false,"given":"Sebastian","family":"Oeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Phillip","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash C.","family":"Mangalhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alva G.","family":"Sainz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-1313","authenticated-orcid":false,"given":"Xiao-Ou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-453X","authenticated-orcid":false,"given":"Qin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Bosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-1158","authenticated-orcid":false,"given":"Parker L.","family":"Sulkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Tripple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Kaech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-5560","authenticated-orcid":false,"given":"Peter M.","family":"Glazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-8717","authenticated-orcid":false,"given":"Gerald S.","family":"Shadel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"150_CR1","doi-asserted-by":"publisher","first-page":"3665","DOI":"10.1074\/jbc.M708444200","volume":"283","author":"DF Bogenhagen","year":"2008","unstructured":"Bogenhagen, D. F., Rousseau, D. & Burke, S. The layered structure of human mitochondrial DNA nucleoids. J. Biol. Chem. 283, 3665\u20133675 (2008).","journal-title":"J. Biol. Chem."},{"key":"150_CR2","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nri2975","volume":"11","author":"AP West","year":"2011","unstructured":"West, A. P., Shadel, G. S. & Ghosh, S. Mitochondria in innate immune responses. Nat. Rev. Immunol. 11, 389\u2013402 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"150_CR3","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nri.2017.21","volume":"17","author":"AP West","year":"2017","unstructured":"West, A. P. & Shadel, G. S. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat. Rev. Immunol. 17, 363\u2013375 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"150_CR4","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nature14156","volume":"520","author":"AP West","year":"2015","unstructured":"West, A. P. et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520, 553\u2013557 (2015).","journal-title":"Nature"},{"key":"150_CR5","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41586-018-0372-z","volume":"560","author":"Z Zhong","year":"2018","unstructured":"Zhong, Z. et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560, 198\u2013203 (2018).","journal-title":"Nature"},{"key":"150_CR6","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.molcel.2019.02.038","volume":"74","author":"LD Aarreberg","year":"2019","unstructured":"Aarreberg, L. D. et al. Interleukin-1\u03b2 induces mtDNA release to activate innate immune signaling via cGAS-STING. Mol. Cell 74, 801\u2013815 (2019). e806.","journal-title":"Mol. Cell"},{"key":"150_CR7","doi-asserted-by":"publisher","first-page":"12196","DOI":"10.1073\/pnas.1708744114","volume":"114","author":"J Bai","year":"2017","unstructured":"Bai, J. et al. DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway. Proc. Natl Acad. Sci. USA 114, 12196\u201312201 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"150_CR8","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","volume":"32","author":"WM Schneider","year":"2014","unstructured":"Schneider, W. M., Chevillotte, M. D. & Rice, C. M. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32, 513\u2013545 (2014).","journal-title":"Annu. Rev. Immunol."},{"key":"150_CR9","doi-asserted-by":"publisher","first-page":"5532","DOI":"10.1128\/JVI.76.11.5532-5539.2002","volume":"76","author":"N Grandvaux","year":"2002","unstructured":"Grandvaux, N. et al. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76, 5532\u20135539 (2002).","journal-title":"J. Virol."},{"key":"150_CR10","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/nri1900","volume":"6","author":"K Honda","year":"2006","unstructured":"Honda, K. & Taniguchi, T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol. 6, 644\u2013658 (2006).","journal-title":"Nat. Rev. Immunol."},{"key":"150_CR11","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.1038\/emboj.2013.203","volume":"32","author":"H Cheon","year":"2013","unstructured":"Cheon, H. et al. IFN\u03b2-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. EMBO J. 32, 2751\u20132763 (2013).","journal-title":"EMBO J."},{"key":"150_CR12","doi-asserted-by":"publisher","first-page":"9373","DOI":"10.1073\/pnas.0903487106","volume":"106","author":"H Cheon","year":"2009","unstructured":"Cheon, H. & Stark, G. R. Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes. Proc. Natl Acad. Sci. USA 106, 9373\u20139378 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"150_CR13","doi-asserted-by":"publisher","first-page":"10443","DOI":"10.1073\/pnas.1513341112","volume":"112","author":"PS Sung","year":"2015","unstructured":"Sung, P. S. et al. Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness. Proc. Natl Acad. Sci. USA 112, 10443\u201310448 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"150_CR14","doi-asserted-by":"publisher","first-page":"18490","DOI":"10.1073\/pnas.0809242105","volume":"105","author":"RR Weichselbaum","year":"2008","unstructured":"Weichselbaum, R. R. et al. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc. Natl Acad. Sci. USA 105, 18490\u201318495 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"150_CR15","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.it.2015.09.007","volume":"36","author":"AJ Minn","year":"2015","unstructured":"Minn, A. J. Interferons and the immunogenic effects of cancer therapy. Trends Immunol. 36, 725\u2013737 (2015).","journal-title":"Trends Immunol."},{"key":"150_CR16","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.molcel.2017.04.028","volume":"66","author":"CS Yang","year":"2017","unstructured":"Yang, C. S. et al. Ubiquitin modification by the E3 ligase\/ADP-ribosyltransferase Dtx3L\/Parp9. Mol. Cell 66, 503\u2013516 (2017). e505.","journal-title":"Mol. Cell"},{"key":"150_CR17","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1128\/MCB.00990-12","volume":"33","author":"Q Yan","year":"2013","unstructured":"Yan, Q. et al. BAL1 and its partner E3 ligase, BBAP, link poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Mol. Cell. Biol. 33, 845\u2013857 (2013).","journal-title":"Mol. Cell. Biol."},{"key":"150_CR18","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.molcel.2009.08.019","volume":"36","author":"Q Yan","year":"2009","unstructured":"Yan, Q. et al. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol. Cell 36, 110\u2013120 (2009).","journal-title":"Mol. Cell"},{"key":"150_CR19","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/ni.3279","volume":"16","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y. et al. PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. Nat. Immunol. 16, 1215\u20131227 (2015).","journal-title":"Nat. Immunol."},{"key":"150_CR20","doi-asserted-by":"publisher","first-page":"5328","DOI":"10.1128\/JVI.00037-14","volume":"88","author":"T Abe","year":"2014","unstructured":"Abe, T. & Barber, G. N. Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-\u03baB activation through TBK1. J. Virol. 88, 5328\u20135341 (2014).","journal-title":"J. Virol."},{"key":"150_CR21","doi-asserted-by":"publisher","first-page":"2640","DOI":"10.1158\/1535-7163.MCT-16-0048","volume":"15","author":"I Buondonno","year":"2016","unstructured":"Buondonno, I. et al. Mitochondria-targeted doxorubicin: a new therapeutic strategy against doxorubicin-resistant osteosarcoma. Mol. Cancer Ther. 15, 2640\u20132652 (2016).","journal-title":"Mol. Cancer Ther."},{"key":"150_CR22","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/pcmr.12591","volume":"30","author":"J Wang","year":"2017","unstructured":"Wang, J. et al. UV-induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell Melanoma Res. 30, 428\u2013435 (2017).","journal-title":"Pigment Cell Melanoma Res."},{"key":"150_CR23","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/nature11003","volume":"483","author":"J Barretina","year":"2012","unstructured":"Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603\u2013607 (2012).","journal-title":"Nature"},{"key":"150_CR24","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0163-7258(92)90033-V","volume":"54","author":"G Singh","year":"1992","unstructured":"Singh, G., Sharkey, S. M. & Moorehead, R. Mitochondrial DNA damage by anticancer agents. Pharmacol. Ther. 54, 217\u2013230 (1992).","journal-title":"Pharmacol. Ther."},{"key":"150_CR25","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/s42255-019-0120-1","volume":"1","author":"RH H\u00e4m\u00e4l\u00e4inen","year":"2019","unstructured":"H\u00e4m\u00e4l\u00e4inen, R. H. et al. Defects in mtDNA replication challenge nuclear genome stability through nucleotide depletion and provide a unifying mechanism for mouse progerias. Nat. Metab. 1, 958\u2013965 (2019).","journal-title":"Nat. Metab."},{"key":"150_CR26","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm.2016.23","volume":"17","author":"PM Quiros","year":"2016","unstructured":"Quiros, P. M., Mottis, A. & Auwerx, J. Mitonuclear communication in homeostasis and stress. Nat. Rev. Mol. Cell Biol. 17, 213\u2013226 (2016).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"150_CR27","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.tcb.2014.11.002","volume":"25","author":"M Scheibye-Knudsen","year":"2015","unstructured":"Scheibye-Knudsen, M., Fang, E. F., Croteau, D. L., Wilson, D. M. III & Bohr, V. A. Protecting the mitochondrial powerhouse. Trends Cell Biol. 25, 158\u2013170 (2015).","journal-title":"Trends Cell Biol."},{"key":"150_CR28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1146\/annurev.biochem.66.1.409","volume":"66","author":"GS Shadel","year":"1997","unstructured":"Shadel, G. S. & Clayton, D. A. Mitochondrial DNA maintenance in vertebrates. Annu. Rev. Biochem. 66, 409\u2013435 (1997).","journal-title":"Annu. Rev. Biochem."},{"key":"150_CR29","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ajpath.2011.10.003","volume":"180","author":"DK Woo","year":"2012","unstructured":"Woo, D. K. et al. Mitochondrial genome instability and ROS enhance intestinal tumorigenesis in APC\nMin\/+ mice. Am. J. Pathol. 180, 24\u201331 (2012).","journal-title":"Am. J. Pathol."},{"key":"150_CR30","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/S0092-8674(00)81289-1","volume":"84","author":"JE Durbin","year":"1996","unstructured":"Durbin, J. E., Hackenmiller, R., Simon, M. C. & Levy, D. E. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84, 443\u2013450 (1996).","journal-title":"Cell"},{"key":"150_CR31","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","volume":"8","author":"FA Ran","year":"2013","unstructured":"Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281\u20132308 (2013).","journal-title":"Nat. Protoc."},{"key":"150_CR32","doi-asserted-by":"publisher","first-page":"e1004654","DOI":"10.1371\/journal.pgen.1004654","volume":"10","author":"MJ Yousefzadeh","year":"2014","unstructured":"Yousefzadeh, M. J. et al. Mechanism of suppression of chromosomal instability by DNA polymerase POLQ. PLoS Genet. 10, e1004654 (2014).","journal-title":"PLoS Genet."},{"key":"150_CR33","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1667\/RR14746.1","volume":"188","author":"S Oeck","year":"2017","unstructured":"Oeck, S. et al. The Focinator v2-0 \u2013 graphical interface, four channels, colocalization analysis and cell phase identification. Radiat. Res. 188, 114\u2013120 (2017).","journal-title":"Radiat. Res."},{"key":"150_CR34","doi-asserted-by":"publisher","DOI":"10.1186\/s13014-015-0453-1","volume":"10","author":"S Oeck","year":"2015","unstructured":"Oeck, S., Malewicz, N. M., Hurst, S., Rudner, J. & Jendrossek, V. The Focinator \u2013 a new open-source tool for high-throughput foci evaluation of DNA damage. Radiat. Oncol. 10, 163 (2015).","journal-title":"Radiat. Oncol."},{"key":"150_CR35","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/978-1-62703-739-6_31","volume":"1105","author":"A Furda","year":"2014","unstructured":"Furda, A., Santos, J. H., Meyer, J. N. & Van Houten, B. Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells. Methods Mol. Biol. 1105, 419\u2013437 (2014).","journal-title":"Methods Mol. Biol."}],"container-title":["Nature Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42255-019-0150-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-019-0150-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-019-0150-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T10:07:34Z","timestamp":1732788454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42255-019-0150-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["150"],"URL":"https:\/\/doi.org\/10.1038\/s42255-019-0150-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737052890.793575902","asserted-by":"object"}]},"ISSN":["2522-5812"],"issn-type":[{"value":"2522-5812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]},"assertion":[{"value":"22 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}