tetano
Editor, Senior Moderator
Nat Commun. 2014 Aug 20;5:4713. doi: 10.1038/ncomms5713.
Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity.
Yoshizumi T1, Ichinohe T2, Sasaki O1, Otera H3, Kawabata S1, Mihara K3, Koshiba T1.
Author information
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 (Δψm). Here we examine the physiological relevance of Δψm 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 Δψm. 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 Δψm 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.
PMID:
25140902
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/25140902
Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity.
Yoshizumi T1, Ichinohe T2, Sasaki O1, Otera H3, Kawabata S1, Mihara K3, Koshiba T1.
Author information
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 (Δψm). Here we examine the physiological relevance of Δψm 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 Δψm. 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 Δψm 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.
PMID:
25140902
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/25140902