Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome

被引：794

作者：

Misawa, Takuma ^{[1
,2
]}

Takahama, Michihiro ^{[1
,2
]}

Kozaki, Tatsuya ^{[1
,2
]}

Lee, Hanna ^{[1
,2
]}

Zou, Jian ^{[1
,2
]}

Saitoh, Tatsuya ^{[1
,2
]}

Akira, Shizuo ^{[1
,2
]}

机构：

[1] Osaka Univ, Host Def Lab, World Premier Int Res Ctr, Immunol Frontier Res Ctr, Osaka, Japan

[2] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 05期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

NALP3; INFLAMMASOME; CATHEPSIN-B; AUTOPHAGY; INHIBITORS; LYSOSOMES; IL-1-BETA; CRYSTALS; DYNAMICS; GOUT;

D O I：

10.1038/ni.2550

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

NLRP3 forms an inflammasome with its adaptor ASC, and its excessive activation can cause inflammatory diseases. However, little is known about the mechanisms that control assembly of the inflammasome complex. Here we show that microtubules mediated assembly of the NLRP3 inflammasome. Inducers of the NLRP3 inflammasome caused aberrant mitochondrial homeostasis to diminish the concentration of the coenzyme NAD(+), which in turn inactivated the NAD(+)-dependent alpha-tubulin deacetylase sirtuin 2; this resulted in the accumulation of acetylated alpha-tubulin. Acetylated alpha-tubulin mediated the dynein-dependent transport of mitochondria and subsequent apposition of ASC on mitochondria to NLRP3 on the endoplasmic reticulum. Therefore, in addition to direct activation of NLRP3, the creation of optimal sites for signal transduction by microtubules is required for activation of the entire NLRP3 inflammasome.

引用

收藏

页码：454 / +

页数：8

相关论文

共 44 条

[1]

MEC-17 is an α-tubulin acetyltransferase [J].

Akella, Jyothi S. ;

Wloga, Dorota ;

Kim, Jihyun ;

Starostina, Natalia G. ;

Lyons-Abbott, Sally ;

Morrissette, Naomi S. ;

Dougan, Scott T. ;

Kipreos, Edward T. ;

Gaertig, Jacek .

NATURE, 2010, 467 (7312) :218-U111

[2]

COLCHICINE HAS OPPOSITE EFFECTS ON INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION [J].

ALLEN, JN ;

HERZYK, DJ ;

WEWERS, MD .

AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (04) :L315-L321

[3]

Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella [J].

Broz, Petr ;

Newton, Kim ;

Lamkanfi, Mohamed ;

Mariathasan, Sanjeev ;

Dixit, Vishva M. ;

Monack, Denise M. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (08) :1745-1755

[4]

Histone deacetylase inhibitors prevent exocytosis of interleukin-1β-containing secretory lysosomes:: role of microtubules [J].

Carta, Sonia ;

Tassi, Sara ;

Semino, Claudia ;

Fossati, Gianluca ;

Mascagni, Paolo ;

Dinarello, Charles A. ;

Rubartelli, Anna .

BLOOD, 2006, 108 (05) :1618-1626

[5]

Tissue-specific regulation of SIRT1 by calorie restriction [J].

Chen, Danica ;

Bruno, Joanne ;

Easlon, Erin ;

Lin, Su-Ju ;

Cheng, Hwei-Ling ;

Alt, Frederick W. ;

Guarente, Leonard .

GENES & DEVELOPMENT, 2008, 22 (13) :1753-1757

[6]

The inflammatory process of gout and its treatment [J].

Cronstein, Bruce N. ;

Terkeltaub, Robert .

ARTHRITIS RESEARCH & THERAPY, 2006, 8 (Suppl 1)

[7]

Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation [J].

Dompierre, Jim P. ;

Godin, Juliette D. ;

Charrin, Benedicte C. ;

Cordelieres, Fabrice P. ;

King, Stephen J. ;

Humbert, Sandrine ;

Saudou, Frederic .

JOURNAL OF NEUROSCIENCE, 2007, 27 (13) :3571-3583

[8]

Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica [J].

Dostert, Catherine ;

Petrilli, Virginie ;

Van Bruggen, Robin ;

Steele, Chad ;

Mossman, Brooke T. ;

Tschopp, Jurg .

SCIENCE, 2008, 320 (5876) :674-677

[9]

NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals [J].

Duewell, Peter ;

Kono, Hajime ;

Rayner, Katey J. ;

Sirois, Cherilyn M. ;

Vladimer, Gregory ;

Bauernfeind, Franz G. ;

Abela, George S. ;

Franchi, Luigi ;

Nunez, Gabriel ;

Schnurr, Max ;

Espevik, Terje ;

Lien, Egil ;

Fitzgerald, Katherine A. ;

Rock, Kenneth L. ;

Moore, Kathryn J. ;

Wright, Samuel D. ;

Hornung, Veit ;

Latz, Eicke .

NATURE, 2010, 464 (7293) :1357-U7

[10]

Small-molecule inhibitors of the AAA plus ATPase motor cytoplasmic dynein [J].

Firestone, Ari J. ;

Weinger, Joshua S. ;

Maldonado, Maria ;

Barlan, Kari ;

Langston, Lance D. ;

O'Donnell, Michael ;

Gelfand, Vladimir I. ;

Kapoor, Tarun M. ;

Chen, James K. .

NATURE, 2012, 484 (7392) :125-129

← 1 2 3 4 5 →