Keeping the immune system in check: A role for mitophagy

Immunology and Cell Biology

Volumn 93, Issue 1, 2015, Pages 3-10

  Lazarou, Michael ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CRYOPYRIN; PARKIN; REACTIVE OXYGEN METABOLITE; INFLAMMASOME; MITOCHONDRIAL PROTEIN; PROTEIN KINASE; PTEN-INDUCED PUTATIVE KINASE; UBIQUITIN PROTEIN LIGASE;

CELL DEATH; CELL FUNCTION; CELL VIABILITY; ENERGY YIELD; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; IMMUNITY; IMMUNOCOMPETENT CELL; IMMUNOSURVEILLANCE; MITOCHONDRION; MITOPHAGY; MOLECULAR MECHANICS; REVIEW; SIGNAL TRANSDUCTION; XENOPHAGY; AUTOPHAGY; CELL SURVIVAL; CYTOLOGY; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; METABOLISM; T LYMPHOCYTE;

AUTOPHAGY; CELL SURVIVAL; ENERGY METABOLISM; GENE EXPRESSION REGULATION; HUMANS; IMMUNE SYSTEM; INFLAMMASOMES; MITOCHONDRIA; MITOCHONDRIAL DEGRADATION; MITOCHONDRIAL PROTEINS; PROTEIN KINASES; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; UBIQUITIN-PROTEIN LIGASES;

EID: 84920531897     PISSN: 08189641     EISSN: 14401711     Source Type: Journal    
DOI: 10.1038/icb.2014.75     Document Type: Review

References (100)

1. Hall CJ, Boyle RH, Astin JW, Flores MV, Oehlers SH, Sanderson LE et al. Immunoresponsive gene 1 augments bactericidal activity of macrophage-lineage cells by regulating beta-oxidation-dependent mitochondrial ROS production. Cell Metab 2013; 18: 265-278.
2. 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.
3. Rugarli EI, Langer T. Mitochondrial quality control: a matter of life and death for neurons. EMBO J 2012; 31: 1336-1349.
4. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 2011; 27: 107-132.
5. Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 2008; 182: 685-701.
6. Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbe S, Clague MJ et al. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 2010; 6: 506-522.
7. Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011; 7: 279-296.
8. Noda NN, Ohsumi Y, Inagaki F. Atg8-family interacting motif crucial for selective autophagy. FEBS Lett 2010; 584: 1379-1385.
9. Birgisdottir AB, Lamark T, Johansen T. The LIR motif-crucial for selective autophagy. J Cell Sci 2013; 126: 3237-3247.
10. Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 2007; 104: 19500-19505.
11. Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 2008; 283: 10892-10903.
12. Liu L, Feng D, Chen G, ChenM, Zheng Q, Song P et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 2012; 14: 177-185.
13. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183: 795-803.
14. Geisler S, Holmström KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 2010; 12: 119-131.
15. Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA 2010; 107: 5018-5023.
16. Fu M, St-Pierre P, Shankar J, Wang PT, Joshi B, Nabi IR. Regulation of mitophagy by the Gp78 E3 ubiquitin ligase. Mol Biol Cell 2013; 24: 1153-1162.
17. Orvedahl A, Sumpter R Jr, Xiao G, Ng A, Zou Z, Tang Y et al. Image-based genomewide siRNA screen identifies selective autophagy factors. Nature 2011; 480: 113-117.
18. Lokireddy S, Wijesoma IW, Teng S, Bonala S, Gluckman PD, McFarlane C et al. The ubiquitin ligase Mul1 induces mitophagy in skeletal muscle in response to musclewasting stimuli. Cell Metab 2012; 16: 613-624.
19. Chu CT, Ji J, Dagda RK, Jiang JF, Tyurina YY, Kapralov AA et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol 2013; 15: 1197-1205.
20. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 2010; 11: 45-51.
21. Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M et al. Essential role for Nix in autophagic maturation of erythroid cells. Nature 2008; 454: 232-235.
22. Zhang J, Loyd MR, Randall MS, Waddell MB, Kriwacki RW, Ney PA. A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. Autophagy 2012; 8: 1325-1332.
23. Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R et al. Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis. J Biol Chem 2013; 288: 1099-1113.
24. Chen G, Han Z, Feng D, Chen Y, Chen L, Wu H et al. A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell 2014; 54: 362-377.
25. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 392: 605-608.
26. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004; 304: 1158-1160.
27. Narendra D, Walker JE, Youle R. Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism. Cold Spring Harb Perspect Biol 2012; 4: 1-19.
28. Vincow ES, Merrihew G, Thomas RE, Shulman NJ, Beyer RP, MacCoss MJ et al. The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc Natl Acad Sci USA 2013; 110: 6400-6405.
29. Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q et al. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 2014; 510: 370-375.
30. Narendra DP, Jin SM, Tanaka A, Suen D-F, Gautier CA, Shen J et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 2010; 8: e1000298.
31. Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RLA, Kim J et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA 2010; 107: 378-383.
32. Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 2010; 189: 211-221.
33. Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP et al. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 2013; 496: 372-376.
34. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet 2011; 20: 1726-1737.
35. Meissner C, Lorenz H, Weihofen A, Selkoe DJ, Lemberg MK. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking. J Neurochem 2011; 117: 856-867.
36. Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH et al. PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 2011; 20: 867-879.
37. Greene AW, Grenier K, Aguileta MA, Muise S, Farazifard R, Haque ME et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep 2012; 13: 378-385.
38. Whitworth AJ, Lee JR, Ho VM, Flick R, Chowdhury R, McQuibban GA. Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin. Dis Model Mech 2008; 1: 168-174 discussion 173.
39. Yamano K, Youle RJ. PINK1 is degraded through the N-end rule pathway. Autophagy 2013; 9: 1758-1769.
40. Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 2010; 191: 933-942.
41. Lazarou M, Jin SM, Kane LA, Youle RJ. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell 2012; 22: 320-333.
42. Okatsu K, Uno M, Koyano F, Go E, Kimura M, Oka T et al. A dimeric PINK1-containing complex on depolarized mitochondria stimulates Parkin recruitment. J Biol Chem 2013; 288: 36372-36384.
43. Hasson SA, Kane LA, Yamano K, Huang CH, Sliter DA, Buehler E et al. High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy. Nature 2013; 504: 291-295.
44. Jin SM, Youle RJ. The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 2013; 9: 1750-1757.
45. Chaugule VK, Burchell L, Barber KR, Sidhu A, Leslie SJ, Shaw GS et al. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J 2011; 30: 2853-2867.
46. Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ. PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol 2013; 200: 163-172.
47. Walden H, Martinez-Torres RJ. Regulation of Parkin E3 ubiquitin ligase activity. Cell Mol Life Sci 2012; 69: 3053-3067.
48. Trempe JF, Sauve V, Grenier K, Seirafi M, Tang MY, Menade M et al. Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science 2013; 340: 1451-1455.
49. Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 2011; 474: 105-108.
50. Iguchi M, Kujuro Y, Okatsu K, Koyano F, Kosako H, Kimura M et al. Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation. J Biol Chem 2013; 288: 22019-22032.
51. Zheng X, Hunter T. Parkin mitochondrial translocation is achieved through a novel catalytic activity coupled mechanism. Cell Res 2013; 23: 886-897.
52. Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2012; 2: 120080.
53. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA et al. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 2014; 205: 143-153.
54. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 2014; 510: 162-166.
55. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K et al. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J 2014; 460: 127-139.
56. Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 2010; 191: 1367-1380.
57. Yoshii SR, Kishi C, Ishihara N, Mizushima N. Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J Biol Chem 2011; 286: 19630-19640.
58. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 2011; 147: 893-906.
59. Lee JY, Nagano Y, Taylor JP, Lim KL, Yao TP. Disease-causing mutations in Parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol 2010; 189: 671-679.
60. Cornelissen T, Haddad D, Wauters F, Van Humbeeck C, Mandemakers W, Koentjoro B et al. The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy. Hum Mol Genet 2014; 23: 5227-5242.
61. Yamano K, Fogel AI, Wang C, van der Bliek AM, Youle RJ. Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy. Elife (Cambridge) 2014; 3: e01612.
62. Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 2010; 6: 1090-1106.
63. Itakura E, Kishi-Itakura C, Koyama-Honda I, Mizushima N. Structures containing Atg9A and the ULK1 complex independently target depolarized mitochondria at initial stages of Parkin-mediated mitophagy. J Cell Sci 2012; 125: 1488-1499.
64. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007; 449: 819-826.
65. Watson RO, Manzanillo PS, Cox JS. Extracellular Mtuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 2012; 150: 803-815.
66. Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 2012; 482: 414-418.
67. Boyle KB, Randow F. The role of 'eat-me' signals and autophagy cargo receptors in innate immunity. Curr Opin Microbiol 2013; 16: 339-348.
68. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 2011; 333: 228-233.
69. von Muhlinen N, Akutsu M, Ravenhill BJ, Foeglein A, Bloor S, Rutherford TJ et al. LC3C, bound selectively by a noncanonical LIR motif in NDP52, is required for antibacterial autophagy. Mol Cell 2012; 48: 329-342.
70. Huett A, Heath RJ, Begun J, Sassi SO, Baxt LA, Vyas JM et al. The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella typhimurium. Cell Host Microbe 2012; 12: 778-790.
71. Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G, Rae CS et al. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature 2013; 501: 512-516.
72. Mira MT, Alcais A, Nguyen VT, Moraes MO, Di Flumeri C, Vu HT et al. Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 2004; 427: 636-640.
73. Ali S, Vollaard AM, Widjaja S, Surjadi C, van de Vosse E, van Dissel JT. PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever. Clin Exp Immunol 2006; 144: 425-431.
74. 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.
75. van Bruggen R, Koker MY, Jansen M, van Houdt M, Roos D, Kuijpers TW et al. Human NLRP3 inflammasome activation is Nox1-4 independent. Blood 2010; 115: 5398-5400.
76. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469: 221-225.
77. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 2011; 12: 222-230.
78. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 2008; 456: 264-268.
79. Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol 2013; 14: 480-488.
80. Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY et al. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med 2011; 208: 519-533.
81. Cordero MD, Alcocer-Gomez E, Culic O, Carrion AM, de Miguel M, Diaz-Parrado E et al. NLRP3 inflammasome is activated in fibromyalgia: the effect of coenzyme Q10. Antioxid Redox Signal 2014; 20: 1169-1180.
82. van der Burgh R, Nijhuis L, Pervolaraki K, Compeer EB, Jongeneel LH, van Gijn M et al. Defects in mitochondrial clearance predispose human monocytes to interleukin-1beta hypersecretion. J Biol Chem 2014; 289: 5000-5012.
83. Dashdorj A, Jyothi KR, Lim S, Jo A, Nguyen MN, Ha J et al. Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines. BMC Med 2013; 11: 178.
84. Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 2012; 485: 251-255.
85. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 2012; 36: 401-414.
86. Allam R, Lawlor KE, Yu EC, Mildenhall AL, Moujalled DM, Lewis RS et al. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep 2014; 15: 982-990.
87. Wang Y, Tong X, Ye X. Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation. J Immunol 2012; 189: 5304-5313.
88. Jenkins K, Khoo JJ, Sadler A, Piganis R, Wang D, Borg NA et al. Mitochondrially localised MUL1 is a novel modulator of antiviral signaling. Immunol Cell Biol 2013; 91: 321-330.
89. Jacobs JL, Zhu J, Sarkar SN, Coyne CB. Regulation of mitochondrial antiviral signaling (MAVS) expression and signaling by the mitochondria-associated endoplasmic reticulum membrane (MAM) protein Gp78. J Biol Chem 2014; 289: 1604-1616.
90. Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA 2009; 106: 2770-2775.
91. Koshiba T, Yasukawa K, Yanagi Y, Kawabata S. Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling. Sci Signal 2011; 4: ra7.
92. Kim SJ, Syed GH, Siddiqui A. Hepatitis C virus induces the mitochondrial translocation of Parkin and subsequent mitophagy. PLoS Pathog 2013; 9: e1003285.
93. Kim SJ, Khan M, Quan J, Till A, Subramani S, Siddiqui A. Hepatitis B virus disrupts mitochondrial dynamics: induces fission and mitophagy to attenuate apoptosis. PLoS Pathog 2013; 9: e1003722.
94. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 2011; 186: 3299-3303.
95. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab 2006; 4: 13-24.
96. Willinger T, Flavell RA. Canonical autophagy dependent on the class III phosphoinositide-3 kinase Vps34 is required for naive T-cell homeostasis. Proc Natl Acad Sci USA 2012; 109: 8670-8675.
97. Pua HH, Guo J, Komatsu M, He YW. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol 2009; 182: 4046-4055.
98. Bell C, English L, Boulais J, Chemali M, Caron-Lizotte O, Desjardins M et al. Quantitative proteomics reveals the induction of mitophagy in tumor necrosis factoralpha-activated (TNFalpha) macrophages. Mol Cell Proteomics 2013; 12: 2394-2407.
99. Rubartelli A. Redox control of NLRP3 inflammasome activation in health and disease. J Leukoc Biol 2012; 92: 951-958.
100. Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA et al. Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 2012; 13: 255-263.