African swine fever virus protein p17 promotes mitophagy by facilitating the interaction of SQSTM1 with TOMM70

ABSTRACT

Viruses have developed different strategies to hijack mitophagy to facilitate their replication. However, whether and how African swine fever virus (ASFV) regulates mitophagy are largely unknown. Here, we found that the ASFV-encoded p17 induced mitophagy. Coimmunoprecipitation/mass spectrometry assays identified translocase of outer mitochondrial membrane 70 (TOMM70) as the protein that interacted with p17. The binding of TOMM70 to p17 promoted the binding of the mitophagy receptor SQSTM1 to TOMM70, led to engulfment of mitochondria by autophagosomes, and consequently decreased the number of mitochondria. Consistently, the levels of TOMM70 and TOMM20 decreased substantially after p17 expression or ASFV infection. Furthermore, p17-mediated mitophagy resulted in the degradation of mitochondrial antiviral signalling proteins and inhibited the production of IFN-α, IL-6 and TNFα. Overall, our findings suggest that ASFV p17 regulates innate immunity by inducing mitophagy via the interaction of SQSTM1 with TOMM70.

KEYWORDS:

• African swine fever virus
• p17
• mitophagy
• TOMM70
• SQSTM1

Acknowledgements

We would like to acknowledge Dr. Changjiang Wen and Dr. Li Huang for kindly providing inactive ASFV infection samples.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data Availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This study is supported by National Natural Science Foundation of China (No. 31941009).