Advanced Review
Mitochondrial RNA, a new trigger of the innate immune system
Joanna Grochowska,
Jolanta Czerwinska,
Lukasz S. Borowski,
Roman J. Szczesny,
Joanna Grochowska
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
Contribution: Conceptualization (equal), Writing - original draft (lead), Writing - review & editing (equal)
Search for more papers by this authorJolanta Czerwinska
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
Contribution: Conceptualization (equal), Writing - original draft (lead), Writing - review & editing (equal)
Search for more papers by this authorLukasz S. Borowski
Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Warsaw, Poland
Contribution: Conceptualization (equal), Funding acquisition (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Roman J. Szczesny
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
Correspondence
Roman J. Szczesny, Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawinskiego 5A, Warsaw, 02-106, Poland.
Email: [email protected]
Contribution: Conceptualization (lead), Funding acquisition (lead), Supervision (lead), Writing - review & editing (lead)
Search for more papers by this authorJoanna Grochowska,
Jolanta Czerwinska,
Lukasz S. Borowski,
Roman J. Szczesny,
Joanna Grochowska
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
Contribution: Conceptualization (equal), Writing - original draft (lead), Writing - review & editing (equal)
Search for more papers by this authorJolanta Czerwinska
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
Contribution: Conceptualization (equal), Writing - original draft (lead), Writing - review & editing (equal)
Search for more papers by this authorLukasz S. Borowski
Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Warsaw, Poland
Contribution: Conceptualization (equal), Funding acquisition (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Roman J. Szczesny
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
Correspondence
Roman J. Szczesny, Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawinskiego 5A, Warsaw, 02-106, Poland.
Email: [email protected]
Contribution: Conceptualization (lead), Funding acquisition (lead), Supervision (lead), Writing - review & editing (lead)
Search for more papers by this authorJoanna Grochowska and Jolanta Czerwinska contributed equally to this study.
Edited by: Jeff Wilusz, Editor-in-Chief
Funding information: Fundacja na rzecz Nauki Polskiej, Grant/Award Number: POIR.04.04.00-00-5E63/18-00; Narodowe Centrum Nauki, Grant/Award Number: 2018/31/D/NZ2/03901
Abstract
Mitochondria play a pivotal role in numerous cellular processes. One of them is regulation of the innate immune pathway. In this instance, mitochondria function in two different aspects of regulatory mechanisms. First, mitochondria are part of the antiviral signaling cascade that is triggered in the cytoplasm and transmitted to effector proteins through mitochondria-localized proteins. Second, mitochondria can become an endogenous source of innate immune stimuli. Under some pathophysiological conditions, mitochondria release to the cytoplasm immunogenic factors, such as mitochondrial nucleic acids. Here, we focus on immunogenic mitochondrial double-stranded RNA (mt-dsRNA) and its origin and metabolism. We discuss factors that are responsible for regulating mt-dsRNA and its escape from mitochondria, emphasizing the contribution of polynucleotide phosphorylase (PNPase, PNPT1). Finally, we review current knowledge of the role of PNPase in human health and disease.
This article is categorized under:
- RNA in Disease and Development > RNA in Disease
Graphical Abstract
Mitochondria act as a double-edged sword when it comes to innate immunity. On the one hand, they help cells to deal with infection; on the other, they can activate sterile immune response by releasing double-stranded RNA. Cells recognize these mislocalized molecules as an enemy and trigger an immune response.
CONFLICT OF INTEREST
The authors have declared no conflicts of interest for this article.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
REFERENCES
- Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013). CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature, 498(7454), 380–384. https://doi.org/10.1038/nature12306
- Alodaib, A., Sobreira, N., Gold, W. A., Riley, L. G., Van Bergen, N. J., Wilson, M. J., Bennetts, B., Thorburn, D. R., Boehm, C., & Christodoulou, J. (2016). Whole-exome sequencing identifies novel variants in PNPT1 causing oxidative phosphorylation defects and severe multisystem disease. European Journal of Human Genetics: EJHG, 25(1), 79–84. https://doi.org/10.1038/ejhg.2016.128
- Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J., Staden, R., & Young, I. G. (1981). Sequence and organization of the human mitochondrial genome. Nature, 290(5806), 457–465. https://doi.org/10.1038/290457a0
- Archibald, J. M. (2015). Endosymbiosis and eukaryotic cell evolution. Current Biology: CB, 25(19), R911–R921. https://doi.org/10.1016/j.cub.2015.07.055
- Balka, K. R., Louis, C., Saunders, T. L., Smith, A. M., Calleja, D. J., D'Silva, D. B., Moghaddas, F., Tailler, M., Lawlor, K. E., Zhan, Y., Burns, C. J., Wicks, I. P., Miner, J. J., Kile, B. T., Masters, S. L., & De Nardo, D. (2020). TBK1 and IKKε act redundantly to mediate STING-induced NF-κB responses in myeloid cells. Cell Reports, 31(1), 107492. https://doi.org/10.1016/j.celrep.2020.03.056
- Bamborschke, D., Kreutzer, M., Koy, A., Koerber, F., Lucas, N., Huenseler, C., Herkenrath, P., Lee-Kirsch, M. A., & Cirak, S. (2021). PNPT1 mutations may cause Aicardi-Goutières-Syndrome. Brain & Development, 43(2), 320–324. https://doi.org/10.1016/j.braindev.2020.10.005
- Bengtsson, A. A., & Rönnblom, L. (2017). Role of interferons in SLE. Best Practice & Research Clinical Rheumatology, 31(3), 415–428. https://doi.org/10.1016/j.berh.2017.10.003
- Berry, M. P. R., Graham, C. M., McNab, F. W., Xu, Z., Bloch, S. A. A., Oni, T., Wilkinson, K. A., Banchereau, R., Skinner, J., Wilkinson, R. J., Quinn, C., Blankenship, D., Dhawan, R., Cush, J. J., Mejias, A., Ramilo, O., Kon, O. M., Pascual, V., Banchereau, J., … O'Garra, A. (2010). An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 466(7309), 973–977. https://doi.org/10.1038/nature09247
- Bolko, L., Jiang, W., Tawara, N., Landon-Cardinal, O., Anquetil, C., Benveniste, O., & Allenbach, Y. (2021). The role of interferons type I, II and III in myositis: A review. Brain Pathology (Zurich, Switzerland), 31(3), e12955. https://doi.org/10.1111/bpa.12955
- Borowski, L. S., Dziembowski, A., Hejnowicz, M. S., Stepien, P. P., & Szczesny, R. J. (2013). Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci. Nucleic Acids Research, 41(2), 1223–1240. https://doi.org/10.1093/nar/gks1130
- Boyapalle, S., Wong, T., Garay, J., Teng, M., San Juan-Vergara, H., Mohapatra, S., & Mohapatra, S. (2012). Respiratory syncytial virus NS1 protein colocalizes with mitochondrial antiviral signaling protein MAVS following infection. PLoS One, 7(2), e29386. https://doi.org/10.1371/journal.pone.0029386
- Brown, G. C. (1992). Control of respiration and ATP synthesis in mammalian mitochondria and cells. The Biochemical Journal, 284, 1–13. https://doi.org/10.1042/bj2840001
- Chen, G. Y., & Nuñez, G. (2010). Sterile inflammation: Sensing and reacting to damage. Nature Reviews Immunology, 10(12), 826–837. https://doi.org/10.1038/nri2873
- Chen, H.-W., Rainey, R. N., Balatoni, C. E., Dawson, D. W., Troke, J. J., Wasiak, S., Hong, J. S., McBride, H. M., Koehler, C. M., Teitell, M. A., & French, S. W. (2006). Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis. Molecular and Cellular Biology, 26(22), 8475–8487. https://doi.org/10.1128/MCB.01002-06
- Coomans de Brachène, A., Castela, A., Musuaya, A. E., Marselli, L., Marchetti, P., & Eizirik, D. L. (2021). Endogenous mitochondrial double-stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells. Autoimmunity Highlights, 12(1), 6. https://doi.org/10.1186/s13317-021-00148-2
- Crow, Y. J., & Manel, N. (2015). Aicardi-Goutières syndrome and the type I interferonopathies. Nature Reviews Immunology, 15(7), 429–440. https://doi.org/10.1038/nri3850
- Darnell, J. E., Kerr, I. M., & Stark, G. R. (1994). Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science (New York, N.Y.), 264(5164), 1415–1421. https://doi.org/10.1126/science.8197455
- de Weerd, N. A., Samarajiwa, S. A., & Hertzog, P. J. (2007). Type I interferon receptors: Biochemistry and biological functions. The Journal of Biological Chemistry, 282(28), 20053–20057. https://doi.org/10.1074/jbc.R700006200
- Dhir, A., Dhir, S., Borowski, L. S., Jimenez, L., Teitell, M., Rötig, A., Crow, Y. J., Rice, G. I., Duffy, D., Tamby, C., Nojima, T., Munnich, A., Schiff, M., de Almeida, C. R., Rehwinkel, J., Dziembowski, A., Szczesny, R. J., & Proudfoot, N. J. (2018). Mitochondrial double-stranded RNA triggers antiviral signalling in humans. Nature, 560(7717), 238–242. https://doi.org/10.1038/s41586-018-0363-0
- Di Caro, V., Walko, T. D., Bola, R. A., Hong, J. D., Pang, D., Hsue, V., Au, A. K., Halstead, E. S., Carcillo, J. A., Clark, R. S. B., & Aneja, R. K. (2016). Plasma mitochondrial DNA: A novel DAMP in pediatric Sepsis. Shock (Augusta, GA), 45(5), 506–511. https://doi.org/10.1097/SHK.0000000000000539
- Ding, S., Zhu, S., Ren, L., Feng, N., Song, Y., Ge, X., Li, B., Flavell, R. A., & Greenberg, H. B. (2018). Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells. eLife, 7. https://doi.org/10.7554/eLife.39494
- Dixit, E., Boulant, S., Zhang, Y., Lee, A. S. Y., Odendall, C., Shum, B., Hacohen, N., Chen, Z. J., Whelan, S. P., Fransen, M., Nibert, M. L., Superti-Furga, G., & Kagan, J. C. (2010). Peroxisomes are signaling platforms for antiviral innate immunity. Cell, 141(4), 668–681. https://doi.org/10.1016/j.cell.2010.04.018
- Eaton, A., Bernier, F. P., Goedhart, C., Caluseriu, O., Lamont, R. E., Boycott, K. M., Parboosingh, J. S., Innes, A. M., & Care4Rare Canada Consortium. (2018). Is PNPT1-related hearing loss ever non-syndromic? Whole exome sequencing of adult siblings expands the natural history of PNPT1-related disorders. American Journal of Medical Genetics: Part A, 176(11), 2487–2493. https://doi.org/10.1002/ajmg.a.40516
- Fang, R., Jiang, Q., Zhou, X., Wang, C., Guan, Y., Tao, J., Xi, J., Feng, J.-M., & Jiang, Z. (2017). MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner. PLoS Pathogens, 13(11), e1006720. https://doi.org/10.1371/journal.ppat.1006720
- Feng, Q., Sekula, D., Guo, Y., Liu, X., Black, C. C., Galimberti, F., Shah, S. J., Sempere, L. F., Memoli, V., Andersen, J. B., Hassel, B. A., Dragnev, K., & Dmitrovsky, E. (2008). UBE1L causes lung cancer growth suppression by targeting cyclin D1. Molecular Cancer Therapeutics, 7(12), 3780–3788. https://doi.org/10.1158/1535-7163.MCT-08-0753
- Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003). IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nature Immunology, 4(5), 491–496. https://doi.org/10.1038/ni921
- Gewartowski, K., Tomecki, R., Muchowski, L., Dmochow Ska, A., Dzwonek, A., Malecki, M., Skurzak, H., Ostrowski, J., & Stepien, P. P. (2006). Up-regulation of human PNPase mRNA by beta-interferon has no effect on protein level in melanoma cell lines. Acta Biochimica Polonica, 53(1), 179–188.
- Grazioli, S., & Pugin, J. (2018). Mitochondrial damage-associated molecular patterns: From inflammatory signaling to human diseases. Frontiers in Immunology, 9, 832. https://doi.org/10.3389/fimmu.2018.00832
- Gresser, I., Morel-Maroger, L., Rivière, Y., Guillon, J. C., Tovey, M. G., Woodrow, D., Sloper, J. C., & Moss, J. (1980). Interferon-induced disease in mice and rats. Annals of the New York Academy of Sciences, 350, 12–20. https://doi.org/10.1111/j.1749-6632.1980.tb20602.x
- Gustafsson, C. M., Falkenberg, M., & Larsson, N.-G. (2016). Maintenance and expression of mammalian mitochondrial DNA. Annual Review of Biochemistry, 85, 133–160. https://doi.org/10.1146/annurev-biochem-060815-014402
- Hajizadeh, S., DeGroot, J., TeKoppele, J. M., Tarkowski, A., & Collins, L. V. (2003). Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis. Arthritis Research & Therapy, 5(5), R234–R240. https://doi.org/10.1186/ar787
- Hensen, F., Potter, A., van Esveld, S. L., Tarrés-Solé, A., Chakraborty, A., Solà, M., & Spelbrink, J. N. (2019). Mitochondrial RNA granules are critically dependent on mtDNA replication factors twinkle and mtSSB. Nucleic Acids Research, 47(7), 3680–3698. https://doi.org/10.1093/nar/gkz047
- Hillen, H. S., Temiakov, D., & Cramer, P. (2018). Structural basis of mitochondrial transcription. Nature Structural & Molecular Biology, 25(9), 754–765. https://doi.org/10.1038/s41594-018-0122-9
- Horner, S. M., Liu, H. M., Park, H. S., Briley, J., & Gale, M. (2011). Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America, 108(35), 14590–14595. https://doi.org/10.1073/pnas.1110133108
- Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., Endres, S., & Hartmann, G. (2006). 5′-Triphosphate RNA is the ligand for RIG-I. Science (New York, N.Y.), 314(5801), 994–997. https://doi.org/10.1126/science.1132505
- Hosseini Bereshneh, A., Rezaei, Z., Jafarinia, E., Rajabi, F., Ashrafi, M. R., Tavasoli, A. R., & Garshasbi, M. (2021). Crystallographic modeling of the PNPT1:C.1453A>G variant as a cause of mitochondrial dysfunction and autosomal recessive deafness; expanding the neuroimaging and clinical features. Mitochondrion, 59, 1–7. https://doi.org/10.1016/j.mito.2021.03.012
- Hou, F., Sun, L., Zheng, H., Skaug, B., Jiang, Q.-X., & Chen, Z. J. (2011). MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell, 146(3), 448–461. https://doi.org/10.1016/j.cell.2011.06.041
- Isaacs, A., & Lindenmann, J. (1957). Virus interference. I. the interferon. Proceedings of the Royal Society of London Series B, Biological Sciences, 147(927), 258–267. https://doi.org/10.1098/rspb.1957.0048
- Ivashkiv, L. B., & Donlin, L. T. (2014). Regulation of type I interferon responses. Nature Reviews Immunology, 14(1), 36–49. https://doi.org/10.1038/nri3581
- Jiang, X., Kinch, L. N., Brautigam, C. A., Chen, X., Du, F., Grishin, N. V., & Chen, Z. J. (2012). Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity, 36(6), 959–973. https://doi.org/10.1016/j.immuni.2012.03.022
- Kang, J., & Pervaiz, S. (2012). Mitochondria: Redox metabolism and dysfunction. Biochemistry Research International, 2012, 896751. https://doi.org/10.1155/2012/896751
- Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005). Suppression of RNA recognition by toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity, 23(2), 165–175. https://doi.org/10.1016/j.immuni.2005.06.008
- Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T. S., Fujita, T., & Akira, S. (2008). Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. The Journal of Experimental Medicine, 205(7), 1601–1610. https://doi.org/10.1084/jem.20080091
- Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005). IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nature Immunology, 6(10), 981–988. https://doi.org/10.1038/ni1243
- Kim, Y., Park, J., Kim, S., Kim, M., Kang, M.-G., Kwak, C., Kang, M., Kim, B., Rhee, H.-W., & Kim, V. N. (2018). PKR senses nuclear and mitochondrial signals by interacting with endogenous double-stranded RNAs. Molecular Cell, 71(6), 1051–1063. https://doi.org/10.1016/j.molcel.2018.07.029
- Komuro, A., & Horvath, C. M. (2006). RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2. Journal of Virology, 80(24), 12332–12342. https://doi.org/10.1128/JVI.01325-06
- Larner, A. C., Chaudhuri, A., & Darnell, J. E. (1986). Transcriptional induction by interferon. New protein(s) determine the extent and length of the induction. The Journal of Biological Chemistry, 261(1), 453–459.
- Lee, J.-H., Shim, Y.-R., Seo, W., Kim, M.-H., Choi, W.-M., Kim, H.-H., Kim, Y. E., Yang, K., Ryu, T., Jeong, J.-M., Choi, H.-G., Eun, H. S., Kim, S.-H., Mun, H., Yoon, J.-H., & Jeong, W.-I. (2020). Mitochondrial double-stranded RNA in exosome promotes Interleukin-17 production through toll-like receptor 3 in alcohol-associated liver injury. Hepatology (Baltimore, MD.), 72(2), 609–625. https://doi.org/10.1002/hep.31041
- Lemaire, P. A., Anderson, E., Lary, J., & Cole, J. L. (2008). Mechanism of PKR activation by dsRNA. Journal of Molecular Biology, 381(2), 351–360. https://doi.org/10.1016/j.jmb.2008.05.056
- Leszczyniecka, M., Kang, D.-C., Sarkar, D., Su, Z.-Z., Holmes, M., Valerie, K., & Fisher, P. B. (2002). Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence. Proceedings of the National Academy of Sciences of the United States of America, 99(26), 16636–16641. https://doi.org/10.1073/pnas.252643699
- Li, X.-D., Sun, L., Seth, R. B., Pineda, G., & Chen, Z. J. (2005). Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proceedings of the National Academy of Sciences of the United States of America, 102(49), 17717–17722. https://doi.org/10.1073/pnas.0508531102
- Lin, C. L., Wang, Y.-T., Yang, W.-Z., Hsiao, Y.-Y., & Yuan, H. S. (2012). Crystal structure of human polynucleotide phosphorylase: Insights into its domain function in RNA binding and degradation. Nucleic Acids Research, 40(9), 4146–4157. https://doi.org/10.1093/nar/gkr1281
- Ling, Z., Tran, K. C., & Teng, M. N. (2009). Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I. Journal of Virology, 83(8), 3734–3742. https://doi.org/10.1128/JVI.02434-08
- Liu, H. M., Loo, Y.-M., Horner, S. M., Zornetzer, G. A., Katze, M. G., & Gale, M. (2012). The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity. Cell Host & Microbe, 11(5), 528–537. https://doi.org/10.1016/j.chom.2012.04.006
- Liu, S., Chen, J., Cai, X., Wu, J., Chen, X., Wu, Y.-T., Sun, L., & Chen, Z. J. (2013). MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. eLife, 2, e00785. https://doi.org/10.7554/eLife.00785
- Liu, T., Zhang, L., Joo, D., & Sun, S.-C. (2017). NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy, 2, 23. https://doi.org/10.1038/sigtrans.2017.23
- Lu, C., Xu, H., Ranjith-Kumar, C. T., Brooks, M. T., Hou, T. Y., Hu, F., Herr, A. B., Strong, R. K., Kao, C. C., & Li, P. (2010). The structural basis of 5′ triphosphate double-stranded RNA recognition by RIG-I C-terminal domain. Structure (London, England: 1993), 18(8), 1032–1043. https://doi.org/10.1016/j.str.2010.05.007
- Lukhele, S., Boukhaled, G. M., & Brooks, D. G. (2019). Type I interferon signaling, regulation and gene stimulation in chronic virus infection. Seminars in Immunology, 43, 101277. https://doi.org/10.1016/j.smim.2019.05.001
- Ma, J., Ketkar, H., Geng, T., Lo, E., Wang, L., Xi, J., Sun, Q., Zhu, Z., Cui, Y., Yang, L., & Wang, P. (2018). Zika virus non-structural protein 4A blocks the RLR-MAVS signaling. Frontiers in Microbiology, 9, 1350. https://doi.org/10.3389/fmicb.2018.01350
- Mao, K., Breen, P., & Ruvkun, G. (2020). Mitochondrial dysfunction induces RNA interference in C. elegans through a pathway homologous to the mammalian RIG-I antiviral response. PLoS Biology, 18(12), e3000996. https://doi.org/10.1371/journal.pbio.3000996
- Martinou, J. C., & Green, D. R. (2001). Breaking the mitochondrial barrier. Nature Reviews Molecular Cell Biology, 2(1), 63–67. https://doi.org/10.1038/35048069
- Matilainen, S., Carroll, C. J., Richter, U., Euro, L., Pohjanpelto, M., Paetau, A., Isohanni, P., & Suomalainen, A. (2017). Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome. Human Molecular Genetics, 26(17), 3352–3361. https://doi.org/10.1093/hmg/ddx221
- McArthur, K., Whitehead, L. W., Heddleston, J. M., Li, L., Padman, B. S., Oorschot, V., Geoghegan, N. D., Chappaz, S., Davidson, S., San Chin, H., Lane, R. M., Dramicanin, M., Saunders, T. L., Sugiana, C., Lessene, R., Osellame, L. D., Chew, T.-L., Dewson, G., Lazarou, M., … Kile, B. T. (2018). BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science (New York, N.Y.), 359(6378), eaao6047. https://doi.org/10.1126/science.aao6047
- McGill, M. R., Staggs, V. S., Sharpe, M. R., Lee, W. M., Jaeschke, H., & Acute Liver Failure Study Group. (2014). Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome. Hepatology (Baltimore, MD.), 60(4), 1336–1345. https://doi.org/10.1002/hep.27265
- Medzhitov, R. (2007). Recognition of microorganisms and activation of the immune response. Nature, 449(7164), 819–826. https://doi.org/10.1038/nature06246
- Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005). Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature, 437(7062), 1167–1172. https://doi.org/10.1038/nature04193
- Minczuk, M., Piwowarski, J., Papworth, M. A., Awiszus, K., Schalinski, S., Dziembowski, A., Dmochowska, A., Bartnik, E., Tokatlidis, K., Stepien, P. P., & Borowski, P. (2002). Localisation of the human hSuv3p helicase in the mitochondrial matrix and its preferential unwinding of dsDNA. Nucleic Acids Research, 30(23), 5074–5086. https://doi.org/10.1093/nar/gkf647
- Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020). The role of mitochondria in neurodegenerative diseases: The lesson from Alzheimer's disease and Parkinson's disease. Molecular Neurobiology, 57(7), 2959–2980. https://doi.org/10.1007/s12035-020-01926-1
- Munday, D. C., Hiscox, J. A., & Barr, J. N. (2010). Quantitative proteomic analysis of A549 cells infected with human respiratory syncytial virus subgroup B using SILAC coupled to LC-MS/MS. Proteomics, 10(23), 4320–4334. https://doi.org/10.1002/pmic.201000228
- Muskardin, T. L. W., & Niewold, T. B. (2018). Type I interferon in rheumatic diseases. Nature Reviews Rheumatology, 14(4), 214–228. https://doi.org/10.1038/nrrheum.2018.31
- Nakahira, K., Kyung, S.-Y., Rogers, A. J., Gazourian, L., Youn, S., Massaro, A. F., Quintana, C., Osorio, J. C., Wang, Z., Zhao, Y., Lawler, L. A., Christie, J. D., Meyer, N. J., Mc Causland, F. R., Waikar, S. S., Waxman, A. B., Chung, R. T., Bueno, R., Rosas, I. O., … Choi, A. M. K. (2013). Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: Derivation and validation. PLoS Medicine, 10(12), e1001577. https://doi.org/10.1371/journal.pmed.1001577
- Ojala, D., Montoya, J., & Attardi, G. (1981). TRNA punctuation model of RNA processing in human mitochondria. Nature, 290(5806), 470–474. https://doi.org/10.1038/290470a0
- Oka, T., Hikoso, S., Yamaguchi, O., Taneike, M., Takeda, T., Tamai, T., Oyabu, J., Murakawa, T., Nakayama, H., Nishida, K., Akira, S., Yamamoto, A., Komuro, I., & Otsu, K. (2012). Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature, 485(7397), 251–255. https://doi.org/10.1038/nature10992
- Onomoto, K., Onoguchi, K., & Yoneyama, M. (2021). Regulation of RIG-I-like receptor-mediated signaling: Interaction between host and viral factors. Cellular & Molecular Immunology, 18(3), 539–555. https://doi.org/10.1038/s41423-020-00602-7
- Pajak, A., Laine, I., Clemente, P., El-Fissi, N., Schober, F. A., Maffezzini, C., Calvo-Garrido, J., Wibom, R., Filograna, R., Dhir, A., Wedell, A., Freyer, C., & Wredenberg, A. (2019). Defects of mitochondrial RNA turnover lead to the accumulation of double-stranded RNA in vivo. PLoS Genetics, 15(7), e1008240. https://doi.org/10.1371/journal.pgen.1008240
- Pang, L.-L., Yuan, X.-H., Shao, C.-S., Li, M.-Z., Wang, Y., Wang, H.-M., Xie, G.-C., Xie, Z.-P., Yuan, Y., Zhou, D.-M., Sun, X.-M., Zhang, Q., Xin, Y., Li, D., & Duan, Z.-J. (2017). The suppression of innate immune response by human rhinovirus C. Biochemical and Biophysical Research Communications, 490(1), 22–28. https://doi.org/10.1016/j.bbrc.2017.05.169
- Paz, S., Vilasco, M., Werden, S. J., Arguello, M., Joseph-Pillai, D., Zhao, T., Nguyen, T. L.-A., Sun, Q., Meurs, E. F., Lin, R., & Hiscott, J. (2011). A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response. Cell Research, 21(6), 895–910. https://doi.org/10.1038/cr.2011.2
- Peisley, A., Wu, B., Xu, H., Chen, Z. J., & Hur, S. (2014). Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature, 509(7498), 110–114. https://doi.org/10.1038/nature13140
- Pennisi, A., Rötig, A., Roux, C.-J., Lévy, R., Henneke, M., Gärtner, J., Teke Kisa, P., Sarioglu, F. C., Yiş, U., Konczal, L. L., Burkardt, D. D., Wu, S., Gaignard, P., Besmond, C., Hubert, L., Rio, M., Barcia, G., Munnich, A., Boddaert, N., & Schiff, M. (2020). Heterogeneity of PNPT1 neuroimaging: Mitochondriopathy, interferonopathy or both? Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2020-107367
- Perng, Y.-C., & Lenschow, D. J. (2018). ISG15 in antiviral immunity and beyond. Nature Reviews Microbiology, 16(7), 423–439. https://doi.org/10.1038/s41579-018-0020-5
- Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006). RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science (New York, N.Y.), 314(5801), 997–1001. https://doi.org/10.1126/science.1132998
- Pietras, Z., Wojcik, M. A., Borowski, L. S., Szewczyk, M., Kulinski, T. M., Cysewski, D., Stepien, P. P., Dziembowski, A., & Szczesny, R. J. (2018a). Controlling the mitochondrial antisense—Role of the SUV3-PNPase complex and its co-factor GRSF1 in mitochondrial RNA surveillance. Molecular & Cellular Oncology, 5(6), e1516452. https://doi.org/10.1080/23723556.2018.1516452
- Pietras, Z., Wojcik, M. A., Borowski, L. S., Szewczyk, M., Kulinski, T. M., Cysewski, D., Stepien, P. P., Dziembowski, A., & Szczesny, R. J. (2018b). Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria. Nature Communications, 9(1), 2558. https://doi.org/10.1038/s41467-018-05007-9
- Platanias, L. C. (2005). Mechanisms of type-I- and type-II-interferon-mediated signalling. Nature Reviews Immunology, 5(5), 375–386. https://doi.org/10.1038/nri1604
- Qin, C., Gu, J., Liu, R., Xu, F., Qian, H., He, Q., & Meng, W. (2017). Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction. Anatolian Journal of Cardiology, 17(3), 224–228. https://doi.org/10.14744/AnatolJCardiol.2016.7209
- Refolo, G., Vescovo, T., Piacentini, M., Fimia, G. M., & Ciccosanti, F. (2020). Mitochondrial interactome: A focus on antiviral signaling pathways. Frontiers in Cell and Developmental Biology, 8, 8. https://doi.org/10.3389/fcell.2020.00008
- Ren, Z., Ding, T., Zuo, Z., Xu, Z., Deng, J., & Wei, Z. (2020). Regulation of MAVS expression and signaling function in the antiviral innate immune response. Frontiers in Immunology, 11, 1030. https://doi.org/10.3389/fimmu.2020.01030
- Rey, T., Zaganelli, S., Cuillery, E., Vartholomaiou, E., Croisier, M., Martinou, J.-C., & Manley, S. (2020). Mitochondrial RNA granules are fluid condensates positioned by membrane dynamics. Nature Cell Biology, 22(10), 1180–1186. https://doi.org/10.1038/s41556-020-00584-8
- Rius, R., Van Bergen, N. J., Compton, A. G., Riley, L. G., Kava, M. P., Balasubramaniam, S., Amor, D. J., Fanjul-Fernandez, M., Cowley, M. J., Fahey, M. C., Koenig, M. K., Enns, G. M., Sadedin, S., Wilson, M. J., Tan, T. Y., Thorburn, D. R., & Christodoulou, J. (2019). Clinical Spectrum and functional consequences associated with bi-allelic pathogenic PNPT1 variants. Journal of Clinical Medicine, 8(11). https://doi.org/10.3390/jcm8112020
- Rone, M. B., Fan, J., & Papadopoulos, V. (2009). Cholesterol transport in steroid biosynthesis: Role of protein-protein interactions and implications in disease states. Biochimica et Biophysica Acta, 1791(7), 646–658. https://doi.org/10.1016/j.bbalip.2009.03.001
- Rusecka, J., Kaliszewska, M., Bartnik, E., & Tońska, K. (2018). Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA. Journal of Applied Genetics, 59(1), 43–57. https://doi.org/10.1007/s13353-017-0424-3
- Sagan, L. (1967). On the origin of mitosing cells. Journal of Theoretical Biology, 14(3), 255–274. https://doi.org/10.1016/0022-5193(67)90079-3
- Saha, S. K., Pietras, E. M., He, J. Q., Kang, J. R., Liu, S.-Y., Oganesyan, G., Shahangian, A., Zarnegar, B., Shiba, T. L., Wang, Y., & Cheng, G. (2006). Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. The EMBO Journal, 25(14), 3257–3263. https://doi.org/10.1038/sj.emboj.7601220
- Saitoh, T., Fujita, N., Hayashi, T., Takahara, K., Satoh, T., Lee, H., Matsunaga, K., Kageyama, S., Omori, H., Noda, T., Yamamoto, N., Kawai, T., Ishii, K., Takeuchi, O., Yoshimori, T., & Akira, S. (2009). Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proceedings of the National Academy of Sciences of the United States of America, 106(49), 20842–20846. https://doi.org/10.1073/pnas.0911267106
- Sarkar, D., Leszczyniecka, M., Kang, D., Lebedeva, I. V., Valerie, K., Dhar, S., Pandita, T. K., & Fisher, P. B. (2003). Down-regulation of Myc as a potential target for growth arrest induced by human polynucleotide phosphorylase (hPNPaseold-35) in human melanoma cells. The Journal of Biological Chemistry, 278(27), 24542–24551. https://doi.org/10.1074/jbc.M302421200
- Sarkar, D., Park, E. S., & Fisher, P. B. (2006). Defining the mechanism by which IFN-beta dowregulates c-myc expression in human melanoma cells: Pivotal role for human polynucleotide phosphorylase (hPNPaseold-35). Cell Death and Differentiation, 13(9), 1541–1553. https://doi.org/10.1038/sj.cdd.4401829
- Sato, R., Arai-Ichinoi, N., Kikuchi, A., Matsuhashi, T., Numata-Uematsu, Y., Uematsu, M., Fujii, Y., Murayama, K., Ohtake, A., Abe, T., & Kure, S. (2018). Novel biallelic mutations in the PNPT1 gene encoding a mitochondrial-RNA-import protein PNPase cause delayed myelination. Clinical Genetics, 93(2), 242–247. https://doi.org/10.1111/cge.13068
- Satoh, T., Kato, H., Kumagai, Y., Yoneyama, M., Sato, S., Matsushita, K., Tsujimura, T., Fujita, T., Akira, S., & Takeuchi, O. (2010). LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proceedings of the National Academy of Sciences of the United States of America, 107(4), 1512–1517. https://doi.org/10.1073/pnas.0912986107
- Schieber, M., & Chandel, N. S. (2014). ROS function in redox signaling and oxidative stress. Current Biology: CB, 24(10), R453–R462. https://doi.org/10.1016/j.cub.2014.03.034
- Schlee, M., Roth, A., Hornung, V., Hagmann, C. A., Wimmenauer, V., Barchet, W., Coch, C., Janke, M., Mihailovic, A., Wardle, G., Juranek, S., Kato, H., Kawai, T., Poeck, H., Fitzgerald, K. A., Takeuchi, O., Akira, S., Tuschl, T., Latz, E., … Hartmann, G. (2009). Recognition of 5′ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity, 31(1), 25–34. https://doi.org/10.1016/j.immuni.2009.05.008
- Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014). Interferon-stimulated genes: A complex web of host defenses. Annual Review of Immunology, 32, 513–545. https://doi.org/10.1146/annurev-immunol-032713-120231
- Schoggins, J. W., & Rice, C. M. (2011). Interferon-stimulated genes and their antiviral effector functions. Current Opinion in Virology, 1(6), 519–525. https://doi.org/10.1016/j.coviro.2011.10.008
- Schoggins, J. W., Wilson, S. J., Panis, M., Murphy, M. Y., Jones, C. T., Bieniasz, P., & Rice, C. M. (2011). A diverse range of gene products are effectors of the type I interferon antiviral response. Nature, 472(7344), 481–485. https://doi.org/10.1038/nature09907
- Scozzi, D., Cano, M., Ma, L., Zhou, D., Zhu, J. H., O'Halloran, J. A., Goss, C., Rauseo, A. M., Liu, Z., Sahu, S. K., Peritore, V., Rocco, M., Ricci, A., Amodeo, R., Aimati, L., Ibrahim, M., Hachem, R., Kreisel, D., Mudd, P. A., … Gelman, A. E. (2021). Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19. JCI Insight, 6(4), 143299. https://doi.org/10.1172/jci.insight.143299
- Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005). Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell, 122(5), 669–682. https://doi.org/10.1016/j.cell.2005.08.012
- Sharma, S., Ten Oever, B. R., Grandvaux, N., Zhou, G.-P., Lin, R., & Hiscott, J. (2003). Triggering the interferon antiviral response through an IKK-related pathway. Science (New York, N.Y.), 300(5622), 1148–1151. https://doi.org/10.1126/science.1081315
- Shaw, A. E., Hughes, J., Gu, Q., Behdenna, A., Singer, J. B., Dennis, T., Orton, R. J., Varela, M., Gifford, R. J., Wilson, S. J., & Palmarini, M. (2017). Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses. PLoS Biology, 15(12), e2004086. https://doi.org/10.1371/journal.pbio.2004086
- Shimada, K., Crother, T. R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V. K., Wolf, A. J., Vergnes, L., Ojcius, D. M., Rentsendorj, A., Vargas, M., Guerrero, C., Wang, Y., Fitzgerald, K. A., Underhill, D. M., Town, T., & Arditi, M. (2012). Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity, 36(3), 401–414. https://doi.org/10.1016/j.immuni.2012.01.009
- Skaug, B., & Assassi, S. (2020). Type I interferon dysregulation in systemic sclerosis. Cytokine, 132, 154635. https://doi.org/10.1016/j.cyto.2018.12.018
- Slavotinek, A. M., Garcia, S. T., Chandratillake, G., Bardakjian, T., Ullah, E., Wu, D., Umeda, K., Lao, R., Tang, P. L.-F., Wan, E., Madireddy, L., Lyalina, S., Mendelsohn, B. A., Dugan, S., Tirch, J., Tischler, R., Harris, J., Clark, M. J., Chervitz, S., … Chen, R. O. (2015). Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. Clinical Genetics, 88(5), 468–473. https://doi.org/10.1111/cge.12543
- Stefan-Lifshitz, M., Karakose, E., Cui, L., Ettela, A., Yi, Z., Zhang, W., & Tomer, Y. (2019). Epigenetic modulation of β cells by interferon-α via PNPT1/mir-26a/TET2 triggers autoimmune diabetes. JCI Insight, 4(5). https://doi.org/10.1172/jci.insight.126663
- Stehling, O., & Lill, R. (2013). The role of mitochondria in cellular iron-sulfur protein biogenesis: Mechanisms, connected processes, and diseases. Cold Spring Harbor Perspectives in Biology, 5(8), a011312. https://doi.org/10.1101/cshperspect.a011312
- Stetson, D. B., & Medzhitov, R. (2006). Type I interferons in host defense. Immunity, 25(3), 373–381. https://doi.org/10.1016/j.immuni.2006.08.007
- Subramanian, N., Natarajan, K., Clatworthy, M. R., Wang, Z., & Germain, R. N. (2013). The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell, 153(2), 348–361. https://doi.org/10.1016/j.cell.2013.02.054
- Sugawara, S., Thomas, D. L., & Balagopal, A. (2019). HIV-1 infection and type 1 interferon: Navigating through uncertain waters. AIDS Research and Human Retroviruses, 35(1), 25–32. https://doi.org/10.1089/AID.2018.0161
- Swenson, S. A., Moore, C. M., Marcero, J. R., Medlock, A. E., Reddi, A. R., & Khalimonchuk, O. (2020). From synthesis to utilization: The ins and outs of mitochondrial heme. Cell, 9(3). https://doi.org/10.3390/cells9030579
- Szczesny, R. J., Borowski, L. S., Brzezniak, L. K., Dmochowska, A., Gewartowski, K., Bartnik, E., & Stepien, P. P. (2010). Human mitochondrial RNA turnover caught in flagranti: Involvement of hSuv3p helicase in RNA surveillance. Nucleic Acids Research, 38(1), 279–298. https://doi.org/10.1093/nar/gkp903
- Szewczyk, M., Malik, D., Borowski, L. S., Czarnomska, S. D., Kotrys, A. V., Klosowska-Kosicka, K., Nowotny, M., & Szczesny, R. J. (2020). Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA. Nucleic Acids Research, 48(10), 5572–5590. https://doi.org/10.1093/nar/gkaa302
- Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Sasaki, S., Imai, K., Shibue, T., Honda, K., & Taniguchi, T. (2003). Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature, 424(6948), 516–523. https://doi.org/10.1038/nature01850
- Tang, E. D., & Wang, C.-Y. (2010). TRAF5 is a downstream target of MAVS in antiviral innate immune signaling. PLoS One, 5(2), e9172. https://doi.org/10.1371/journal.pone.0009172
- Teles, R. M. B., Graeber, T. G., Krutzik, S. R., Montoya, D., Schenk, M., Lee, D. J., Komisopoulou, E., Kelly-Scumpia, K., Chun, R., Iyer, S. S., Sarno, E. N., Rea, T. H., Hewison, M., Adams, J. S., Popper, S. J., Relman, D. A., Stenger, S., Bloom, B. R., Cheng, G., & Modlin, R. L. (2013). Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science (New York, N.Y.), 339(6126), 1448–1453. https://doi.org/10.1126/science.1233665
- Tigano, M., Vargas, D. C., Tremblay-Belzile, S., Fu, Y., & Sfeir, A. (2021). Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature, 591(7850), 477–481. https://doi.org/10.1038/s41586-021-03269-w
- Timmermans, K., Kox, M., Scheffer, G. J., & Pickkers, P. (2016). Plasma nuclear and mitochondrial DNA levels, and markers of inflammation, shock, and organ damage in patients with septic shock. Shock (Augusta, GA), 45(6), 607–612. https://doi.org/10.1097/SHK.0000000000000549
- van Diepen, A., Brand, H. K., Sama, I., Lambooy, L. H. J., van den Heuvel, L. P., van der Well, L., Huynen, M., Osterhaus, A. D. M. E., Andeweg, A. C., & Hermans, P. W. M. (2010). Quantitative proteome profiling of respiratory virus-infected lung epithelial cells. Journal of Proteomics, 73(9), 1680–1693. https://doi.org/10.1016/j.jprot.2010.04.008
- Vandecasteele, G., Szabadkai, G., & Rizzuto, R. (2001). Mitochondrial calcium homeostasis: Mechanisms and molecules. IUBMB Life, 52, 213–219. https://doi.org/10.1080/15216540152846028
- Vazquez, C., & Horner, S. M. (2015). MAVS coordination of antiviral innate immunity. Journal of Virology, 89(14), 6974–6977. https://doi.org/10.1128/JVI.01918-14
- Vedrenne, V., Gowher, A., De Lonlay, P., Nitschke, P., Serre, V., Boddaert, N., Altuzarra, C., Mager-Heckel, A.-M., Chretien, F., Entelis, N., Munnich, A., Tarassov, I., & Rötig, A. (2012). Mutation in PNPT1, which encodes a polyribonucleotide nucleotidyltransferase, impairs RNA import into mitochondria and causes respiratory-chain deficiency. American Journal of Human Genetics, 91(5), 912–918. https://doi.org/10.1016/j.ajhg.2012.09.001
- Venø, S. T., Witt, M. B., Kulikowicz, T., Bohr, V. A., & Stevnsner, T. (2015). Regulation of the human Suv3 helicase on DNA by inorganic cofactors. Biochimie, 108, 160–168. https://doi.org/10.1016/j.biochi.2014.11.003
- von Ameln, S., Wang, G., Boulouiz, R., Rutherford, M. A., Smith, G. M., Li, Y., Pogoda, H.-M., Nürnberg, G., Stiller, B., Volk, A. E., Borck, G., Hong, J. S., Goodyear, R. J., Abidi, O., Nürnberg, P., Hofmann, K., Richardson, G. P., Hammerschmidt, M., Moser, T., … Kubisch, C. (2012). A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. American Journal of Human Genetics, 91(5), 919–927. https://doi.org/10.1016/j.ajhg.2012.09.002
- Wallace, D. C. (2012). Mitochondria and cancer. Nature Reviews Cancer, 12(10), 685–698. https://doi.org/10.1038/nrc3365
- Walsh, D., McCarthy, J., O'Driscoll, C., & Melgar, S. (2013). Pattern recognition receptors—Molecular orchestrators of inflammation in inflammatory bowel disease. Cytokine & Growth Factor Reviews, 24(2), 91–104. https://doi.org/10.1016/j.cytogfr.2012.09.003
- West, A. P., Brodsky, I. E., Rahner, C., Woo, D. K., Erdjument-Bromage, H., Tempst, P., Walsh, M. C., Choi, Y., Shadel, G. S., & Ghosh, S. (2011). TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature, 472(7344), 476–480. https://doi.org/10.1038/nature09973
- West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., Kaech, S. M., Smiley, J. R., Means, R. E., Iwasaki, A., & Shadel, G. S. (2015). Mitochondrial DNA stress primes the antiviral innate immune response. Nature, 520(7548), 553–557. https://doi.org/10.1038/nature14156
- West, A. P., Shadel, G. S., & Ghosh, S. (2011). Mitochondria in innate immune responses. Nature Reviews Immunology, 11(6), 389–402. https://doi.org/10.1038/nri2975
- White, M. J., McArthur, K., Metcalf, D., Lane, R. M., Cambier, J. C., Herold, M. J., van Delft, M. F., Bedoui, S., Lessene, G., Ritchie, M. E., Huang, D. C. S., & Kile, B. T. (2014). Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell, 159(7), 1549–1562. https://doi.org/10.1016/j.cell.2014.11.036
- Wiatrek, D. M., Candela, M. E., Sedmík, J., Oppelt, J., Keegan, L. P., & O'Connell, M. A. (2019). Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein. RNA (New York, N.Y.), 25(6), 713–726. https://doi.org/10.1261/rna.069625.118
- Wilson, E. B., Yamada, D. H., Elsaesser, H., Herskovitz, J., Deng, J., Cheng, G., Aronow, B. J., Karp, C. L., & Brooks, D. G. (2013). Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science (New York, N.Y.), 340(6129), 202–207. https://doi.org/10.1126/science.1235208
- Wu, B., Peisley, A., Tetrault, D., Li, Z., Egelman, E. H., Magor, K. E., Walz, T., Penczek, P. A., & Hur, S. (2014). Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I. Molecular Cell, 55(4), 511–523. https://doi.org/10.1016/j.molcel.2014.06.010
- Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., & Chen, Z. J. (2013). Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science (New York, N.Y.), 339(6121), 826–830. https://doi.org/10.1126/science.1229963
- Xu, L.-G., Wang, Y.-Y., Han, K.-J., Li, L.-Y., Zhai, Z., & Shu, H.-B. (2005). VISA is an adapter protein required for virus-triggered IFN-beta signaling. Molecular Cell, 19(6), 727–740. https://doi.org/10.1016/j.molcel.2005.08.014
- Yamanouchi, S., Kudo, D., Yamada, M., Miyagawa, N., Furukawa, H., & Kushimoto, S. (2013). Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: Time course and the association with clinical status. Journal of Critical Care, 28(6), 1027–1031. https://doi.org/10.1016/j.jcrc.2013.05.006
- Yao, Y., Liu, Z., Jallal, B., Shen, N., & Rönnblom, L. (2013). Type I interferons in Sjögren's syndrome. Autoimmunity Reviews, 12(5), 558–566. https://doi.org/10.1016/j.autrev.2012.10.006
- Young, P. G., & Attardi, G. (1975). Characterization of double-stranded RNA from HeLa cell mitochondria. Biochemical and Biophysical Research Communications, 65(4), 1201–1207. https://doi.org/10.1016/s0006-291x(75)80357-3
- Zevini, A., Olagnier, D., & Hiscott, J. (2017). Crosstalk between cytoplasmic RIG-I and STING sensing pathways. Trends in Immunology, 38(3), 194–205. https://doi.org/10.1016/j.it.2016.12.004
- Zhang, J.-Z., Liu, Z., Liu, J., Ren, J.-X., & Sun, T.-S. (2014). Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue. International Journal of Molecular Medicine, 33(4), 817–824. https://doi.org/10.3892/ijmm.2014.1650
- Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 464(7285), 104–107. https://doi.org/10.1038/nature08780
- Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011). A role for mitochondria in NLRP3 inflammasome activation. Nature, 469(7329), 221–225. https://doi.org/10.1038/nature09663
