The Matrix Protein of Human Parainfluenza Virus Type 3 Induces Mitophagy that Suppresses Interferon Responses

Publication date: 12 April 2017
Source:Cell Host & Microbe, Volume 21, Issue 4
Author(s): Binbin Ding, Linliang Zhang, Zhifei Li, Yi Zhong, Qiaopeng Tang, Yali Qin, Mingzhou Chen
Mitophagy is a form of autophagy that selectively removes damaged mitochondria. Impaired mitochondria can be tagged by the kinase PINK1, which triggers recruitment of the E3-ubiquitin ligase Parkin and subsequent mitochondrial sequestration within autophagosomes. We previously found that human parainfluenza virus type 3 (HPIV3) infection induces autophagy, but the type and mechanisms of autophagy induction remain unknown. Here, we show that matrix protein (M) of HPIV3 translocates to mitochondria and interacts with Tu translation elongation factor mitochondrial (TUFM). M-mediated mitophagy does not require the Parkin-PINK1 pathway but rather an interaction between M and the LC3 protein that mediates autophagosome formation. These interactions with both TUFM and LC3 are required for the induction of mitophagy and lead to inhibition of the type I interferon response. These results reveal that a viral protein is sufficient to induce mitophagy by bridging autophagosomes and mitochondria.

Graphical abstract

Teaser

Mitophagy can selectively remove damaged mitochondria. Ding et al. demonstrate that human parainfluenza virus type 3 (HPIV3) matrix protein (M) induces mitophagy via interactions with mitochondrial elongation factor TUFM and autophagy protein LC3. This M-mediated mitophagy is Parkin-PINK1 independent and inhibits the type I IFN response.


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