DOI QR코드

DOI QR Code

The Relationship between Mitochondria and NLRP3 Inflammasome

  • Lee, Hyun Ah (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Na, Hee Sam (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Chung, Jin (Department of Oral Microbiology, School of Dentistry, Pusan National University)
  • Received : 2017.08.16
  • Accepted : 2017.09.06
  • Published : 2017.09.30

Abstract

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

Keywords

References

  1. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87:99-163. DOI:10.1152/physrev.00013.2006.
  2. Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G. Molecular mechanisms of necroptosis: An ordered cellular explosion. Nat Rev Mol Cell Biol. 2010;11:700-714. DOI: 10.1038/nrm2970.
  3. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, Choi AM. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011;12:222-230. DOI:10.1038/ni.1980.
  4. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221-225. DOI:10.1038/nature09663.
  5. Kepp O, Galluzzi L, Kroemer G. Mitochondrial control of the NLRP3 inflammasome. Nat Immunol. 2011;12:199-200. DOI:10.1038/ni0311-199.
  6. Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell. 2010;140:798-804. DOI:10.1016/j.cell.2010.02.015.
  7. Kawai TAkira S. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol. 2009;21:317-337. DOI: 10.1093/intimm/dxp017.
  8. Anand PK, Malireddi RK, Kanneganti TD. Role of the NLRP3 inflammasome in microbial infection. Front Microbiol. 2011;2:12. DOI:10.3389/fmicb.2011.00012.
  9. Gurung P, Lukens JR, Kanneganti TD. Mitochondria: Diversity in the regulation of the NLRP3 inflammasome. Trends Mol Med. 2015;21:193-201. DOI:10.1016/j.molmed.2014.11.008.
  10. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11:136-140. DOI:10.1038/ni.1831.
  11. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and Irf 3. Cell. 2005;122:669-682. DOI:10.1016/j.cell.2005.08.012.
  12. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. IPS-1, an adaptor triggering RIG-I- and MDA5-mediated type I interferon induction. Nat Immunol. 2005;6:981-988. DOI:10.1038/ni1243.
  13. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. Visa is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19:727-740. DOI:10.1016/j.molcel.2005.08.014.
  14. Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through NALP3 inflammasome sensing of asbestos and silica. Science. 2008;320:674-677. DOI:10.1126/science.1156995.
  15. Chinopoulos C, Adam-Vizi V. Mitochondrial $Ca^{2+}$ sequestration and precipitation revisited. FEBS J. 2010;277:3637-3651. DOI:10.1111/j.1742-4658.2010.07755.x.
  16. Brough D, Le Feuvre RA, Wheeler RD, Solovyova N, Hilfiker S, Rothwell NJ, Verkhratsky A. $Ca^{2+}$ stores and $Ca^{2+}$ entry differentially contribute to the release of IL-1 beta and IL-1 alpha from murine macrophages. J Immunol. 2003;170:3029-3036. DOI:10.4049/jimmunol.170.6.3029.
  17. Lee HM, Yuk JM, Kim KH, Jang J, Kang G, Park JB, Son JW, Jo EK. Mycobacterium abscessus activates the NLRP3 inflammasome via dectin-1-syk and p62/sqstm1. Immunol Cell Biol. 2012;90:601-610. DOI:10.1038/icb.2011.72.
  18. Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, Di Virgilio F. The P2X7 receptor: A key player in IL-1 processing and release. J Immunol. 2006;176:3877-3883. DOI:10.4049/jimmunol.176.7.3877.
  19. Chu J, Thomas LM, Watkins SC, Franchi L, Nunez G, Salter RD. Cholesterol-dependent cytolysins induce rapid release of mature IL-1beta from murine macrophages in a NLRP3 inflammasome and cathepsin b-dependent manner. J Leukoc Biol. 2009;86:1227-1238. DOI:10.1189/jlb.0309164.
  20. Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007;17:1140-1145. DOI: 10.1016/j.cub.2007.05.074.
  21. Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, Germain RN, Kastner DL, Chae JJ. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and camp. Nature. 2012;492:123-127. DOI:10.1038/nature11588.
  22. Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, Horng T. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A. 2012;109:11282-11287. DOI:10.1073/pnas.1117765109.
  23. Belenky P, Bogan KL, Brenner C. NAD+ metabolism in health and disease. Trends Biochem Sci. 2007;32:12-19. DOI:10.1016/j.tibs.2006.11.006.
  24. Misawa T, Takahama M, Kozaki T, Lee H, Zou J, Saitoh T, Akira S. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 2013;14:454-460. DOI:10.1016/j.tibs.2006.11.006.
  25. Arias-Cartin R, Grimaldi S, Arnoux P, Guigliarelli B, Magalon A. Cardiolipin binding in bacterial respiratory complexes: Structural and functional implications. Biochim Biophys Acta. 2012;1817:1937-1949. DOI: 10.1016/j.bbabio.2012.04.005.
  26. Huang Z, Jiang J, Tyurin VA, Zhao Q, Mnuskin A, Ren J, Belikova NA, Feng W, Kurnikov IV, Kagan VE. Cardiolipin deficiency leads to decreased cardiolipin peroxidation and increased resistance of cells to apoptosis. Free Radic Biol Med. 2008;44:1935-1944. DOI:10.1016/j.freeradbiomed.2008.02.016.
  27. Iyer SS, He Q, Janczy JR, Elliott EI, Zhong Z, Olivier AK, Sadler JJ, Knepper-Adrian V, Han R, Qiao L, Eisenbarth SC, Nauseef WM, Cassel SL, Sutterwala FS. Mitochondrial cardiolipin is required for NLRP3 inflammasome activation. Immunity. 2013;39:311-323. DOI:10.1016/j.immuni.2013.08.001.
  28. Chen H, Chomyn A, Chan DC. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem. 2005;280:26185-26192. DOI:10.1074/jbc.M503062200.
  29. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins MFN1 and MFN2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160:189-200. DOI:10.1083/jcb.200211046.
  30. 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 U S A. 2013;110:17963-17968. DOI: 10.1073/pnas.1312571110.
  31. Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH, Franchi L, Whitfield J, Barchet W, Colonna M, Vandenabeele P, Bertin J, Coyle A, Grant EP, Akira S, Nunez G. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/NALP3. Nature. 2006;440:233-236. DOI:10.1038/nature04517.
  32. Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, Wu J, Datta P, McCormick M, Huang L, McDermott E, Eisenlohr L, Landel CP, Alnemri ES. The AIM2 inflammasome is critical for innate immunity to francisella tularensis. Nat Immunol. 2010;11:385-393. DOI:10.1038/ni.1859.
  33. Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E, Hornung V, Vogel SN, Szomolanyi-Tsuda E, Fitzgerald KA. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol. 2010;11:395-402. DOI:10.1038/ni.1864.
  34. Patrushev M, Kasymov V, Patrusheva V, Ushakova T, Gogvadze V, Gaziev AI. Release of mitochondrial DNA fragments from brain mitochondria of irradiated mice. Mitochondrion. 2006;6:43-47. DOI: 10.1016/j.mito.2005.12.001.
  35. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial damps cause inflammatory responses to injury. Nature. 2010;464:104-107. DOI:10.1038/nature08780.
  36. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, Ramanujan VK, Wolf AJ, Vergnes L, Ojcius DM, Rentsendorj A, Vargas M, Guerrero C, Wang Y, Fitzgerald KA, Underhill DM, Town T, Arditi M. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401-414. DOI:10.1016/j.immuni.2012.01.009.
  37. Cruz CM, Rinna A, Forman HJ, Ventura AL, Persechini PM, Ojcius DM. Atp activates a reactive oxygen speciesdependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem. 2007;282:2871-2879. DOI:10.1074/jbc.M608083200.
  38. Subramanian N, Natarajan K, Clatworthy MR, Wang Z, Germain RN. The adaptor mavs promotes NLRP3 mitochondrial localization and inflammasome activation. Cell. 2013;153:348-361. DOI:10.1016/j.cell.2013.02.054.
  39. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, Tsujimura T, Takeuchi O, Yoshimori T, Akira S. Loss of the autophagy protein atg16l1 enhances endotoxininduced IL-1beta production. Nature. 2008;456:264-268. DOI:10.1038/nature07383.
  40. Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J, Huang G, Green M, Kundu M, Chi H, Xavier RJ, Green DR, Lamkanfi M, Dinarello CA, Doherty PC, Kanneganti TD. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol. 2013;14:480-488. DOI:10.1038/ni.2563.
  41. Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, Ferguson DJ, Campbell BJ, Jewell D, Simmons A. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 2010;16:90-97. DOI:10.1038/nm.2069.
  42. Joo JH, Dorsey FC, Joshi A, Hennessy-Walters KM, Rose KL, McCastlain K, Zhang J, Iyengar R, Jung CH, Suen DF, Steeves MA, Yang CY, Prater SM, Kim DH, Thompson CB, Youle RJ, Ney PA, Cleveland JL, Kundu M. Hsp90-cdc37 chaperone complex regulates ULK1- and atg13-mediated mitophagy. Mol Cell. 2011;43:572-585. DOI:10.1016/j.molcel.2011.06.018.