Influenza a virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity

Takuma Yoshizumi, Takeshi Ichinohe, Osamu Sasaki, Hidenori Otera, Shun-Ichiro Kawabata, Katsuyoshi Mihara, Takumi Koshiba

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Mitochondria contribute to cellular innate immunity against RNA viruses. Mitochondrial-mediated innate immunity is regulated by signalling molecules that are recruited to the mitochondrial membrane, and depends on the mitochondrial inner membrane potential (Î "Ï ̂ m). Here we examine the physiological relevance of Î "Ï ̂ m and the mitochondrial-associating influenza A viral protein PB1-F2 in innate immunity. When expressed in host cells, PB1-F2 completely translocates into the mitochondrial inner membrane space via Tom40 channels, and its accumulation accelerates mitochondrial fragmentation due to reduced Î "Ï ̂ m. By contrast, PB1-F2 variants lacking a C-terminal polypeptide, which is frequently found in low pathogenic subtypes, do not affect mitochondrial function. PB1-F2-mediated attenuation of Î "Ï ̂ m suppresses the RIG-I signalling pathway and activation of NLRP3 inflammasomes. PB1-F2 translocation into mitochondria strongly correlates with impaired cellular innate immunity, making this translocation event a potential therapeutic target.

Original languageEnglish
Article number4713
JournalNature communications
Volume5
DOIs
Publication statusPublished - Aug 20 2014

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influenza
Mitochondria
mitochondria
immunity
viruses
Viruses
Innate Immunity
proteins
Membranes
Mitochondrial Membranes
membranes
Cellular Immunity
Inflammasomes
Proteins
Viral Proteins
Mitochondrial Membrane Potential
RNA Viruses
polypeptides
Chemical activation
RNA

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Influenza a virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. / Yoshizumi, Takuma; Ichinohe, Takeshi; Sasaki, Osamu; Otera, Hidenori; Kawabata, Shun-Ichiro; Mihara, Katsuyoshi; Koshiba, Takumi.

In: Nature communications, Vol. 5, 4713, 20.08.2014.

Research output: Contribution to journalArticle

Yoshizumi, Takuma ; Ichinohe, Takeshi ; Sasaki, Osamu ; Otera, Hidenori ; Kawabata, Shun-Ichiro ; Mihara, Katsuyoshi ; Koshiba, Takumi. / Influenza a virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. In: Nature communications. 2014 ; Vol. 5.
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AU - Kawabata, Shun-Ichiro

AU - Mihara, Katsuyoshi

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