Research Papers:

CSFV induced mitochondrial fission and mitophagy to inhibit apoptosis

Hongchao Gou, Mingqiu Zhao, Hailuan Xu, Jin Yuan, Wencheng He, Mengjiao Zhu, Hongxing Ding, Lin Yi and Jinding Chen _

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Oncotarget. 2017; 8:39382-39400. https://doi.org/10.18632/oncotarget.17030

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Hongchao Gou1,*, Mingqiu Zhao1,*, Hailuan Xu1, Jin Yuan1, Wencheng He1, Mengjiao Zhu1, Hongxing Ding1, Lin Yi1 and Jinding Chen1

1College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Jinding Chen, email: [email protected]

Keywords: classical swine fever virus (CSFV), mitochondrial fission, mitophagy, apoptosis

Received: August 17, 2016     Accepted: March 17, 2017     Published: April 11, 2017


Classical swine fever virus (CSFV), which causes typical clinical characteristics in piglets, including hemorrhagic syndrome and immunosuppression, is linked to hepatitis C and dengue virus. Oxidative stress and a reduced mitochondrial transmembrane potential are disturbed in CSFV-infected cells. The balance of mitochondrial dynamics is essential for cellular homeostasis. In this study, we offer the first evidence that CSFV induces mitochondrial fission and mitophagy to inhibit host cell apoptosis for persistent infection. The formation of mitophagosomes and decline in mitochondrial mass relevant to mitophagy were detected in CSFV-infected cells. CSFV infection increased the expression and mitochondrial translocation of Pink and Parkin. Upon activation of the PINK1 and Parkin pathways, Mitofusin 2 (MFN2), a mitochondrial fusion mediator, was ubiquitinated and degraded in CSFV-infected cells. Mitophagosomes and mitophagolysosomes induced by CSFV were, respectively, observed by the colocalization of LC3-associated mitochondria with Parkin or lysosomes. In addition, a sensitive dual fluorescence reporter (mito-mRFP-EGFP) was utilized to analyze the delivery of mitophagosomes to lysosomes. Mitochondrial fission caused by CSFV infection was further determined by mitochondrial fragmentation and Drp1 translocation into mitochondria using a confocal microscope. The preservation of mitochondrial proteins, upregulated apoptotic signals and decline of viral replication resulting from the silencing of Drp1 and Parkin in CSFV-infected cells suggested that CSFV induced mitochondrial fission and mitophagy to enhance cell survival and viral persistence. Our data for mitochondrial fission and selective mitophagy in CSFV-infected cells reveal a unique view of the pathogenesis of CSFV infection and provide new avenues for the development of antiviral strategies.

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