tetano
Editor, Senior Moderator
Autophagy. 2020 Feb 3. doi: 10.1080/15548627.2020.1725375. [Epub ahead of print] [h=1]Influenza A virus protein PB1-F2 impairs innate immunity by inducing mitophagy.[/h]
Wang R[SUP]1,[/SUP][SUP]2[/SUP], Zhu Y[SUP]1,[/SUP][SUP]2[/SUP], Ren C[SUP]1,[/SUP][SUP]2[/SUP], Yang S[SUP]1,[/SUP][SUP]2[/SUP], Tian S[SUP]1,[/SUP][SUP]2[/SUP], Chen H[SUP]1,[/SUP][SUP]2[/SUP], Jin M[SUP]1,[/SUP][SUP]2[/SUP], Zhou H[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV) infection induces mitophagy, which is essential for the clearance of damaged mitochondria. Dysfunctional mitochondria can be selectively targeted by PINK1, which recruits PRKN/PARK2 and leads to subsequent mitochondrial sequestration within autophagosomes. The IAV PB1-F2 protein translocates to mitochondria, accelerates the mitochondrial fragmentation and impairs the innate immunity. However, whether PB1-F2 mediates IAV-induced mitophagy and the relation between mitophagy and PB1-F2-attenuated innate immunity remain obscure. Here, we showed that PB1-F2 translocated to mitochondria by interacting and colocalizing with TUFM (Tu translation elongation factor, mitochondrial). Further studies revealed that PB1-F2 induced complete mitophagy, which required the interactions of PB1-F2 with both TUFM and MAP1LC3B/LC3B that mediated the autophagosome formation. PB1-F2-induced mitophagy was critical for the MAVS (mitochondrial antiviral signaling protein) degradation and led to its suppression of the type I IFN production. Importantly, the C-terminal LIR motif of PB1-F2 protein was demonstrated to be essential for its mitophagy induction and attenuated innate immunity. In conclusion, PB1-F2-induced mitophagy strongly correlates with impaired cellular innate immunity, revealing it is a potential therapeutic target.
[h=4]KEYWORDS:[/h] LC3B; MAVS; TUFM; influenza PB1-F2 protein; innate immunity; mitophagy
PMID: 32013669 DOI: 10.1080/15548627.2020.1725375
Wang R[SUP]1,[/SUP][SUP]2[/SUP], Zhu Y[SUP]1,[/SUP][SUP]2[/SUP], Ren C[SUP]1,[/SUP][SUP]2[/SUP], Yang S[SUP]1,[/SUP][SUP]2[/SUP], Tian S[SUP]1,[/SUP][SUP]2[/SUP], Chen H[SUP]1,[/SUP][SUP]2[/SUP], Jin M[SUP]1,[/SUP][SUP]2[/SUP], Zhou H[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV) infection induces mitophagy, which is essential for the clearance of damaged mitochondria. Dysfunctional mitochondria can be selectively targeted by PINK1, which recruits PRKN/PARK2 and leads to subsequent mitochondrial sequestration within autophagosomes. The IAV PB1-F2 protein translocates to mitochondria, accelerates the mitochondrial fragmentation and impairs the innate immunity. However, whether PB1-F2 mediates IAV-induced mitophagy and the relation between mitophagy and PB1-F2-attenuated innate immunity remain obscure. Here, we showed that PB1-F2 translocated to mitochondria by interacting and colocalizing with TUFM (Tu translation elongation factor, mitochondrial). Further studies revealed that PB1-F2 induced complete mitophagy, which required the interactions of PB1-F2 with both TUFM and MAP1LC3B/LC3B that mediated the autophagosome formation. PB1-F2-induced mitophagy was critical for the MAVS (mitochondrial antiviral signaling protein) degradation and led to its suppression of the type I IFN production. Importantly, the C-terminal LIR motif of PB1-F2 protein was demonstrated to be essential for its mitophagy induction and attenuated innate immunity. In conclusion, PB1-F2-induced mitophagy strongly correlates with impaired cellular innate immunity, revealing it is a potential therapeutic target.
[h=4]KEYWORDS:[/h] LC3B; MAVS; TUFM; influenza PB1-F2 protein; innate immunity; mitophagy
PMID: 32013669 DOI: 10.1080/15548627.2020.1725375