Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling

Takumi Koshiba, Kai Yasukawa, Yusuke Yanagi, Shun-Ichiro Kawabata

研究成果: ジャーナルへの寄稿記事

108 引用 (Scopus)

抄録

Mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. Mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called MAVS (mitochondrial antiviral signaling). We found that cells that lack the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection, resulting in increased viral replication. In contrast, cells with null mutations in either Mfn1 or Mfn2 retained their RLR-induced antiviral responses. We also found that a reduced mitochondrial membrane potential (ΔΨm) correlated with the reduced antiviral response. The dissipation in ΔΨm did not affect the activation of the transcription factor interferon regulatory factor 3 downstream of MAVS, which suggests that ΔΨm and MAVS are coupled at the same stage in the RLR signaling pathway. Our results provide evidence that the physiological function of mitochondria plays a key role in innate antiviral immunity.

元の言語英語
記事番号ra7
ジャーナルScience Signaling
4
発行部数158
DOI
出版物ステータス出版済み - 2 1 2011

Fingerprint

Mitochondrial Membrane Potential
Antiviral Agents
Membranes
Mitochondria
Innate Immunity
Fusion reactions
Chemical activation
Interferon Regulatory Factor-3
Mitochondrial Dynamics
Null Lymphocytes
Mammals
Mitochondrial Proteins
Eukaryotic Cells
Virus Diseases
Tretinoin
Cellular Immunity
Organelles
Interferons
Immunity
Membrane Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling. / Koshiba, Takumi; Yasukawa, Kai; Yanagi, Yusuke; Kawabata, Shun-Ichiro.

:: Science Signaling, 巻 4, 番号 158, ra7, 01.02.2011.

研究成果: ジャーナルへの寄稿記事

@article{b6d958949928451c813cb316379924e2,
title = "Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling",
abstract = "Mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. Mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called MAVS (mitochondrial antiviral signaling). We found that cells that lack the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection, resulting in increased viral replication. In contrast, cells with null mutations in either Mfn1 or Mfn2 retained their RLR-induced antiviral responses. We also found that a reduced mitochondrial membrane potential (ΔΨm) correlated with the reduced antiviral response. The dissipation in ΔΨm did not affect the activation of the transcription factor interferon regulatory factor 3 downstream of MAVS, which suggests that ΔΨm and MAVS are coupled at the same stage in the RLR signaling pathway. Our results provide evidence that the physiological function of mitochondria plays a key role in innate antiviral immunity.",
author = "Takumi Koshiba and Kai Yasukawa and Yusuke Yanagi and Shun-Ichiro Kawabata",
year = "2011",
month = "2",
day = "1",
doi = "10.1126/scisignal.2001147",
language = "English",
volume = "4",
journal = "Science Signaling",
issn = "1937-9145",
publisher = "American Association for the Advancement of Science",
number = "158",

}

TY - JOUR

T1 - Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling

AU - Koshiba, Takumi

AU - Yasukawa, Kai

AU - Yanagi, Yusuke

AU - Kawabata, Shun-Ichiro

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. Mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called MAVS (mitochondrial antiviral signaling). We found that cells that lack the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection, resulting in increased viral replication. In contrast, cells with null mutations in either Mfn1 or Mfn2 retained their RLR-induced antiviral responses. We also found that a reduced mitochondrial membrane potential (ΔΨm) correlated with the reduced antiviral response. The dissipation in ΔΨm did not affect the activation of the transcription factor interferon regulatory factor 3 downstream of MAVS, which suggests that ΔΨm and MAVS are coupled at the same stage in the RLR signaling pathway. Our results provide evidence that the physiological function of mitochondria plays a key role in innate antiviral immunity.

AB - Mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. Mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called MAVS (mitochondrial antiviral signaling). We found that cells that lack the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection, resulting in increased viral replication. In contrast, cells with null mutations in either Mfn1 or Mfn2 retained their RLR-induced antiviral responses. We also found that a reduced mitochondrial membrane potential (ΔΨm) correlated with the reduced antiviral response. The dissipation in ΔΨm did not affect the activation of the transcription factor interferon regulatory factor 3 downstream of MAVS, which suggests that ΔΨm and MAVS are coupled at the same stage in the RLR signaling pathway. Our results provide evidence that the physiological function of mitochondria plays a key role in innate antiviral immunity.

UR - http://www.scopus.com/inward/record.url?scp=79551716551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551716551&partnerID=8YFLogxK

U2 - 10.1126/scisignal.2001147

DO - 10.1126/scisignal.2001147

M3 - Article

VL - 4

JO - Science Signaling

JF - Science Signaling

SN - 1937-9145

IS - 158

M1 - ra7

ER -