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 journalArticlepeer-review

168 Citations (Scopus)


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
Publication statusPublished - Aug 20 2014

All Science Journal Classification (ASJC) codes

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


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