PKM2 induces mitophagy through the AMPK-mTOR pathway promoting CSFV proliferation

• DOI: 10.1128/jvi.01751-23
• Publication Date: 2024-02-06T14:00:18Z
• Authors: Xiaodi Liu; Quanhui Yan; Xueyi Liu; Wenkang Wei; Linke Zou; Feifan Zhao; Sen Zeng; Lin Yi; Hongxing Ding; Mingqiu Zhao; Jinding Chen; Shuangqi Fan
• Keywords: PKM2; NS5A

ABSTRACT Viruses exploit the host cell’s energy metabolism system to support their replication. Mitochondria, known as powerhouse of cell, play a critical role in regulating cell survival and virus Our prior research indicated that classical swine fever (CSFV) alters mitochondrial dynamics triggers glycolytic metabolic reprogramming. However, mechanism PKM2, key regulatory enzyme metabolism, CSFV replication remain unclear. In this study, we discovered enhances PKM2 expression utilizes inhibit pyruvate production. Using an affinity purification coupled mass spectrometry system, successfully identified PKM novel interaction partner non-structural protein NS4A. Furthermore, validated between both NS4A NS5A through co-immunoprecipitation confocal analysis. was found promote NS5A. Moreover, observed induces mitophagy by activating AMPK-mTOR signaling pathway, thereby facilitating proliferation. summary, our data reveal whereby enzyme, promotes proliferation inducing mitophagy. These findings offer new avenue for developing antiviral strategies. IMPORTANCE rely on material-energy replication, disorders subsequent immunosuppression—a major contributor persistent viral infections. Classical is no exception. severe acute infectious disease caused CSFV, resulting significant economic losses global pig industry. While (pyruvate dehydrogenase) pathway tumor cells has been extensively studied, its involvement infection remains relatively unknown. unveil which mediates infection, offering avenues development