Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production

被引：146

作者：

Amini, Poorya ^{[1
]}

Stojkov, Darko ^{[1
]}

Felser, Andrea ^{[2
]}

Jackson, Christopher B. ^{[3
]}

Courage, Carolina ^{[4
,5
]}

Schaller, Andre ^{[4
,5
]}

Gelman, Laurent ^{[6
]}

Soriano, Maria Eugenia ^{[7
]}

Nuoffer, Jean-Marc ^{[2
]}

Scorrano, Luca ^{[8
]}

Benarafa, Charaf ^{[9
,10
]}

Yousefi, Shida ^{[1
]}

Simon, Hans-Uwe ^{[1
]}

机构：

[1] Univ Bern, Inst Pharmacol, CH-3010 Bern, Switzerland

[2] Bern Univ Hosp, Univ Inst Clin Chem, CH-3010 Bern, Switzerland

[3] Univ Helsinki, Biomedicum Helsinki, Res Program Mol Neurol, FIN-00290 Helsinki, Finland

[4] Univ Bern, Div Human Genet, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland

[5] Univ Bern, Dept Pediat, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland

[6] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[7] Univ Padua, Dept Biol, I-35121 Padua, Italy

[8] VIMM, I-35129 Padua, Italy

[9] Inst Virol & Immunol, CH-3147 Mittelhausern, Switzerland

[10] Univ Bern, Vetsuisse Fac, Dept Infect Dis & Pathol, CH-3012 Bern, Switzerland

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

瑞士国家科学基金会;

关键词：

DOMINANT OPTIC ATROPHY; MITOCHONDRIAL-DNA; OPA1; MUTATIONS; BACTERIAL CLEARANCE; SKELETAL-MUSCLE; NADPH OXIDASE; FUSION; RELEASE; DEGRANULATION; METABOLISM;

D O I：

10.1038/s41467-018-05387-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1(N Delta)), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD(+) availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1(N Delta) mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.

引用

页数：16

共 62 条

[1]

A splice site mutation in the murine OpaI gene features pathology of autosomal dominant optic atrophy [J].

Alavi, Marcel V. ;

Bette, Stefanie ;

Schimpf, Simone ;

Schuettauf, Frank ;

Schraermeyer, Ulrich ;

Wehrl, Hans F. ;

Ruttiger, Lukas ;

Beck, Susanne C. ;

Tonagel, Felix ;

Pichler, Bernd J. ;

Knipper, Marlies ;

Peters, Thomas ;

Laufs, Juergen ;

Wissinger, Bernd .

BRAIN, 2007, 130 :1029-1042

[2]

OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28 [J].

Alexander, C ;

Votruba, M ;

Pesch, UEA ;

Thiselton, DL ;

Mayer, S ;

Moore, A ;

Rodriguez, M ;

Kellner, U ;

Leo-Kottler, B ;

Auburger, G ;

Bhattacharya, SS ;

Wissinger, B .

NATURE GENETICS, 2000, 26 (02) :211-215

[3]

OPA1 mutations induce mitochondrial DNA instability and optic atrophy plus phenotypes [J].

Amati-Bonneau, Patrizia ;

Valentino, Maria Lucia ;

Reynier, Pascal ;

Gallardo, Maria Esther ;

Bornstein, Belen ;

Boissiere, Anne ;

Campos, Yolanda ;

Rivera, Henry ;

de la Aleja, Jesus Gonzalez ;

Carroccia, Rosanna ;

Iommarini, Luisa ;

Labauge, Pierre ;

Figarella-Branger, Dominique ;

Marcorelles, Pascale ;

Furby, Alain ;

Beauvais, Katell ;

Letournel, Franck ;

Liguori, Rocco ;

La Morgia, Chiara ;

Montagna, Pasquale ;

Liguori, Maria ;

Zanna, Claudia ;

Rugolo, Michela ;

Cossarizza, Andrea ;

Wissinger, Bernd ;

Verny, Christophe ;

Schwarzenbacher, Robert ;

Martin, Miguel Angel ;

Arenas, Joaquin ;

Ayuso, Carmen ;

Garesse, Rafael ;

Lenaers, Guy ;

Bonneau, Dominique ;

Carelli, Valerio .

BRAIN, 2008, 131 :338-351

[4]

OPA1-associated disorders: Phenotypes and pathophysiology [J].

Amati-Bonneau, Patrizia ;

Milea, Dan ;

Bonneau, Dominique ;

Chevrollier, Arnaud ;

Ferre, Marc ;

Guillet, Virginie ;

Gueguen, Naig ;

Loiseau, Dominique ;

de Crescenzo, Marie-Anne Pou ;

Verny, Christophe ;

Procaccio, Vincent ;

Lenaers, Guy ;

Reynier, Pascal .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2009, 41 (10) :1855-1865

[5]

NET formation can occur independently of RIPK3 and MLKL signaling [J].

Amini, Poorya ;

Stojkov, Darko ;

Wang, Xiaoliang ;

Wicki, Simone ;

Kaufmann, Thomas ;

Wong, Wendy Wei-Lynn ;

Simon, Hans-Uwe ;

Yousefi, Shida .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2016, 46 (01) :178-184

[6]

Neutrophil Function: From Mechanisms to Disease [J].

Amulic, Borko ;

Cazalet, Christel ;

Hayes, Garret L. ;

Metzler, Kathleen D. ;

Zychlinsky, Arturo .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 30, 2012, 30 :459-489

[7]

Mitochondrial Dynamics - Mitochondrial Fission and Fusion in Human Diseases [J].

Archer, Stephen L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (23) :2236-2251

[8]

Mitochondria Regulate Neutrophil Activation by Generating ATP for Autocrine Purinergic Signaling [J].

Bao, Yi ;

Ledderose, Carola ;

Seier, Thomas ;

Graf, Amelie F. ;

Brix, Bianca ;

Chong, Eritza ;

Junger, Wolfgang G. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (39) :26794-26803

[9]

Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke [J].

Basilico, Paola ;

Cremona, Tiziana P. ;

Oevermann, Anna ;

Piersigilli, Alessandra ;

Benarafa, Charaf .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2016, 54 (03) :424-435

[10]

The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection [J].

Benarafa, Charaf ;

Priebe, Gregory P. ;

Remold-O'Donnell, Eileen .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1901-1909

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