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RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway

Nature Immunology volume 15, pages 1126–1133 (2014)Cite this article

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Abstract

The NLRP3 inflammasome functions as a crucial component of the innate immune system in recognizing viral infection, but the mechanism by which viruses activate this inflammasome remains unclear. Here we found that inhibition of the serine-threonine kinases RIP1 (RIPK1) or RIP3 (RIPK3) suppressed RNA virus–induced activation of the NLRP3 inflammasome. Infection with an RNA virus initiated assembly of the RIP1-RIP3 complex, which promoted activation of the GTPase DRP1 and its translocation to mitochondria to drive mitochondrial damage and activation of the NLRP3 inflammasome. Notably, the RIP1-RIP3 complex drove the NLRP3 inflammasome independently of MLKL, an essential downstream effector of RIP1-RIP3–dependent necrosis. Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus–induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways.

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Figure 1: Role of RIP3 in RNA virus–induced activation of the NLRP3 inflammasome.
Figure 2: Role of RIP3 in virus-induced activation of the NLRP3 inflammasome in vivo.
Figure 3: RNA virus–induced activation of the NLRP3 inflammasome depends on RIP1 but not on MLKL.
Figure 4: The RIP1-RIP3 complex is required for mitochondrial damage and the translocation of ASC to mitochondria during infection with an RNA virus.
Figure 5: The RIP1-RIP3 complex promotes RNA virus–induced activation of DRP1.
Figure 6: Role of DRP1 in RNA virus–induced mitochondrial damage and activation of the NLRP3 inflammasome.
Figure 7: dsRNA activates the NLRP3 inflammasome in a RIP1–, RIP3– and DRP1-dependent manner.

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References

  1. Chen, G., Shaw, M.H., Kim, Y.G. & Nunez, G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu. Rev. Pathol. 4, 365–398 (2009).

    Article  CAS  PubMed  Google Scholar 

  2. Martinon, F., Mayor, A. & Tschopp, J. The inflammasomes: guardians of the body. Annu. Rev. Immunol. 27, 229–265 (2009).

    Article  CAS  PubMed  Google Scholar 

  3. Davis, B.K., Wen, H. & Ting, J.P. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol. 29, 707–735 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhou, R., Yazdi, A.S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Iyer, S.S. et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39, 311–323 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Misawa, T. et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 14, 454–460 (2013).

    Article  CAS  PubMed  Google Scholar 

  7. Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847–856 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Muñoz-Planillo, R. et al. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38, 1142–1153 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Muruve, D.A. et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452, 103–107 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Thomas, P.G. et al. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 30, 566–575 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kanneganti, T.D. Central roles of NLRs and inflammasomes in viral infection. Nat. Rev. Immunol. 10, 688–698 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514–518 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ichinohe, T., Lee, H.K., Ogura, Y., Flavell, R. & Iwasaki, A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med. 206, 79–87 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Allen, I.C. et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556–565 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rajan, J.V., Rodriguez, D., Miao, E.A. & Aderem, A. The NLRP3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection. J. Virol. 85, 4167–4172 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kanneganti, T.D. et al. Critical role for cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J. Biol. Chem. 281, 36560–36568 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Ichinohe, T., Pang, I.K. & Iwasaki, A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat. Immunol. 11, 404–410 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rajan, J.V., Warren, S.E., Miao, E.A. & Aderem, A. Activation of the NLRP3 inflammasome by intracellular poly I:C. FEBS Lett. 584, 4627–4632 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang, D.W. et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325, 332–336 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. He, S. et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100–1111 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. Cho, Y.S. et al. Phosphorylation-driven assembly of the RIP1–RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137, 1112–1123 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kang, T.B., Yang, S.H., Toth, B., Kovalenko, A. & Wallach, D. Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome. Immunity 38, 27–40 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. Vince, J.E. et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 36, 215–227 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Yabal, M. et al. XIAP Restricts TNF- and RIP3-dependent cell death and inflammasome activation. Cell Rep. 7, 1796–1808 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. Philip, N.H. et al. Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling. Proc. Natl. Acad. Sci. USA 111, 7385–7390 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Weng, D. et al. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. Proc. Natl. Acad. Sci. USA 111, 7391–7396 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lukens, J.R. et al. RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3. Nature 498, 224–227 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Takahashi, N. et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 3, e437 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sun, L. et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213–227 (2012).

    Article  CAS  PubMed  Google Scholar 

  30. Wang, Z., Jiang, H., Chen, S., Du, F. & Wang, X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148, 228–243 (2012).

    Article  CAS  PubMed  Google Scholar 

  31. Ichinohe, T., Yamazaki, T., Koshiba, T. & Yanagi, Y. Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after RNA virus infection. Proc. Natl. Acad. Sci. USA 110, 17963–17968 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shimada, K. et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36, 401–414 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nakahira, K. et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12, 222–230 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Lupfer, C. et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat. Immunol. 14, 480–488 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stout-Delgado, H.W., Vaughan, S.E., Shirali, A.C., Jaramillo, R.J. & Harrod, K.S. Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin. J. Immunol. 188, 2815–2824 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. Knott, A.B., Perkins, G., Schwarzenbacher, R. & Bossy-Wetzel, E. Mitochondrial fragmentation in neurodegeneration. Nat. Rev. Neurosci. 9, 505–518 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Losón, O.C., Song, Z., Chen, H. & Chan, D.C. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol. Biol. Cell 24, 659–667 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ishihara, N. et al. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat. Cell Biol. 11, 958–966 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. Poeck, H. et al. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production. Nat. Immunol. 11, 63–69 (2010).

    Article  CAS  PubMed  Google Scholar 

  40. Mitoma, H. et al. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 39, 123–135 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Janeway, C.A. Jr. & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Ryu, S.W., Jeong, H.J., Choi, M., Karbowski, M. & Choi, C. Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation. Cell. Mol. Life Sci. 67, 2839–2850 (2010).

    Article  CAS  PubMed  Google Scholar 

  43. Moujalled, D.M., Cook, W.D., Murphy, J.M. & Vaux, D.L. Necroptosis induced by RIPK3 requires MLKL but not Drp1. Cell Death Dis. 5, e1086 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Martinon, F., Petrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237–241 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Newton, K., Sun, X. & Dixit, V.M. Kinase RIP3 is dispensable for normal NF-κBs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol. Cell. Biol. 24, 1464–1469 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kato, H. et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity 23, 19–28 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Gitlin, L. et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc. Natl. Acad. Sci. USA 103, 8459–8464 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wu, J. et al. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 23, 994–1006 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Alexopoulou, L., Holt, A.C., Medzhitov, R. & Flavell, R.A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Yan, Y. et al. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity 38, 1154–1163 (2013).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank J. Tschopp (University of Lausanne) for Nlrp3−/− mice; S. Akira (Osaka University) for Rig-I−/− mice; V.M. Dixit (Genentech) for Rip3−/− mice; M. Colonna (Washington University) for Mda5−/− mice; Z. Jiang (Peking University) for Sendai virus and VSV (Indiana strain); and Z. Song (Wuhan University) for the DRP1 construct. Supported by the National Basic Research Program of China (2014CB910800), the National Natural Science Foundation of China (81330078 and 81222040), the Doctoral Fund of the Ministry of Education of China (20123402120001, 20123402110010), the One Hundred Person Project (R.Z.) and the Fundamental Research Funds for the Central Universities (R.Z. and W.J.).

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  1. Xiaqiong Wang and Wei Jiang: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China

    Xiaqiong Wang, Wei Jiang, Yiqing Yan, Tao Gong, Zhigang Tian & Rongbin Zhou

  2. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Innovation Center for Cell Biology, Xiamen University, Xiamen, Fujian, China.,

    Jiahuai Han

  3. Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China

    Zhigang Tian & Rongbin Zhou

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Contributions

X.W., W.J., Y.Y. and T.G. performed the experiments; W.J., J.H., Z.T. and R.Z. designed the research; X.W., W.J., Z.T. and R.Z. wrote the manuscript; and R.Z. and Z.T. supervised the project.

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Correspondence to Zhigang Tian or Rongbin Zhou.

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Integrated supplementary information

Supplementary Figure 1 Role of RIP1-RIP3 and PGAM5 in RNA virus–induced inflammasome activation.

(a) LDH release from LPS-primed BMDMs from wild-type mice (WT), Rip3-/-or Nlrp3-/-mice infected with VSV for 6 hours or stimulated with nigericin for 30 min. (b) qPCR analysis of Ifn-β expression in non-primed BMDMs from WT, Rip3-/- or Nlrp3-/- mice infected with VSV as indicated doses for 6 hours. (c) Immunoblot analysis of RIP1 expression in BMDMs transfected with siRNA against Rip1 for 48 hours. (d) Immunoblot analysis of pro-IL-1β or NLRP3 expression in BMDMs transfected with siRNA against Rip1 and stimulated with Pam3CSK4 for 6 hours. (e) Immunoblot analysis of PGAM5 in THP-1 cells stably expressing shRNA against PGAM5. (f, g) IL-1β secretion from THP-1 cells stably expressing shRNA against PGAM5 infected with VSV for 6 hours (f), or stimulated with MSU for 4 hours or nigericin for 30 min (g). (h) Confocal microscopy analysis in LPS-primed BMDMs from Rip3+/+ or Rip3-/-mice infected with VSV for 2 hours or stimulated with nigericin for 30 min, and then stained with MitoSOX and DAPI. Scale bar, 50 μm. (i) Confocal microscopy analysis in LPS-primed BMDMs pretreated with Nec-1s (30 μM) for 1 hour and then infected with VSV for 2 hours or stimulated with nigericin for 30 min. After treatment, the cells were stained with MitoSOX and DAPI. Scale bar, 50 μm. NS, P > 0.05 (two-way ANOVA (a,b,f,g). Data are representative of at three independent experiments (c-e, h, i) or are from three independent experiments (with biological duplicates in each) (a, b, f, g; mean and s.e.m.).

Supplementary Figure 2 RIP3 is required for VSV-induced translocation of ASC to mitochondria.

Confocal microscopy analysis in LPS-primed BMDMs from Rip3+/+ or Rip3-/- mice infected with VSV for 2 hours and then stained with anti-ASC antibody, Mitotracker red and DAPI. Data are representative of at three independent experiments.

Supplementary Figure 3 RIP3 is required for VSV-induced translocation of DRP1 to mitochondria.

Confocal microscopy analysis in LPS-primed BMDMs from Rip3+/+ or Rip3-/- mice infected with VSV for 2 hours or stimulated with nigericin for 30 min, and then stained with anti-DRP1 antibody, Mitotracker and DAPI. Scale bar, 20 μm. Data are representative of at three independent experiments.

Supplementary Figure 4 RIP1 is required for VSV-induced translocation of DRP1 to mitochondria.

Confocal microscopy analysis in LPS-primed BMDMs pretreated with Nec-1s (30 μM) for 1 hour and then were infected with VSV for 2 hours or stimulated with nigericin for 30 min. After treatment, the cells were stained with anti-DRP1 antibody, Mitotracker and DAPI. Scale bar, 20 μm. Data are representative of at three independent experiments

Supplementary Figure 5 MLKL is not required for VSV-induced translocation of DRP1 to mitochondria.

Confocal microscopy analysis in LPS-primed BMDMs from Mlkl+/+ or Mlkl-/- mice were infected with VSV for 2 hours or stimulated with nigericin for 30 min, and then stained with anti-DRP1 antibody and Mitotracker. Scale bar, 20 μm. Data are representative of at three independent experiments.

Supplementary Figure 6 Role of DRP1 or FIS1 in mitochondrial damage and inflammasome activation.

(a) Immunoblot analysis of BMDMs transfected with siRNA against Drp1 for 48 hours. (b) Confocal microscopy analysis of LPS-primed BMDMs transfected with siRNA against Drp1 and then infected with VSV for 2 hours or stimulated with nigericin for 30 min and followed by staining with MitoSOX and DAPI. Scale bar, 50 μm. (c) IL-1β secretion from LPS-primed BMDMs transfected with siRNA against Drp1 and then stimulated with MSU, poly (A:T) for 4 hours or ATP, nigericin for 30 min. (d) Immunoblot analysis of BMDMs transfected with siRNA against Fis1 for 48 hours. (e, f) Confocal microscopy analysis of LPS-primed BMDMs transfected with siRNA against Fis1 and infected with VSV for 2 hours or stimulated with nigericin for 30 min and followed by staining with Mitotracker red. Representative pictures (e) or qualification (f) was shown. Scale bar, 50 μm. * P < 0.001, NS P > 0.05. Data are representative of at three independent experiments (a, b, d, e) or are from three independent experiments (with biological duplicates in each) (c, f; mean and s.e.m.).

Supplementary Figure 7 Role of RIP3 and DRP1 in CCCP-induced mitochondrial fission and IL-1β production.

(a) Immunoblot analysis of DRP1 phosphorylation in LPS-primed BMDMs stimulated with CCCP (10 μM) or infected with VSV for 1 hours. (b) IL-1β secretion from LPS-primed BMDMs from Rip3+/+ or Rip3-/-mice were stimulated with CCCP for 5 hours. (c) Confocal microscopy analysis of LPS-primed BMDMs from Rip3+/+ or Rip3-/- mice stimulated with CCCP (10 μM) for 2 hours, and then stained with anti-DRP1 antibody and Mitotracker. Scale bar, 25 μm. (d) IL-1β secretion from LPS-primed BMDMs transfected with siRNA against Drp1 and then stimulated with CCCP (10 μM) for 5 hours. (e, f) Confocal microscopy analysis of LPS-primed BMDMs transfected with siRNA against Drp1 and stimulated with CCCP (10 μM) for 2 hours, and followed by staining with Mitotracker red and DAPI. Representative pictures (e) or qualification (f) was shown. Scale bar, 25 μm. NS P > 0.05, * P<0.01 (two-way ANOVA), * P<0.001 (two-way ANOVA). Data are representative of at three independent experiments (a, c, e) or are from three independent experiments (with biological duplicates in each) (b, d, f; mean and s.e.m.).

Supplementary Figure 8 Role of RNA sensors in VSV- or dsRNA-induced activation of the NLRP3 inflammasome.

(a, b) IL-1β secretion from LPS-primed BMDMs from wild-type mice, Rig-I-/- or Mda5-/- mice infected with VSV (a) or transfected with poly (I:C) (b) for 6 hours. (c) qPCR analysis of Ifn-β expression in non-primed BMDMs from wild-type mice, Rig-I-/- or Mda5-/- mice infected with VSV for 6 hours. (d) Immunoblot analysis of THP-1 cells stably expressing shRNA against Rip1 or DHX33. (e) IL-1β secretion from THP-1 cells stably expressing shRNA against Rip1 or DHX33 infected with VSV for 6 hours or stimulated with nigericin for 30 min. (f, g) IL-1β secretion from Pam3CSK4-primed BMDMs from Tlr3+/+ or Tlr3-/-mice infected with VSV (f) or stimulated with poly (I:C) transfection (g) for 6 hours. NS P > 0.05 (unpaired t-test (a, b, c, g), NS P > 0.05 (two-way ANOVA (f)), * P < 0.01 (two-way ANOVA (e)), ** P < 0.001 (two-way ANOVA (c)). Data are representative of at three independent experiments (d) or are from three independent experiments (with biological duplicates in each) (a-c, e-g; mean and s.e.m.).

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Wang, X., Jiang, W., Yan, Y. et al. RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway. Nat Immunol 15, 1126–1133 (2014). https://doi.org/10.1038/ni.3015

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