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Mitophagy in TGEV infection counteracts oxidative stress and apoptosis
Liqi Zhu1, Chunxiao Mou1, Xing Yang1
1Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
Abstract:
The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.
Insights
Transmissible gastroenteritis virus (TGEV) triggers mitophagy, a cellular process, in pigs to reduce oxidative stress and apoptosis. This mechanism may aid cell survival and viral infection.
Area of Science:
- Cell Biology
- Virology
- Molecular Biology
Background:
- Intestinal epithelial cells rely on mitochondria for absorption and barrier function.
- Mitophagy is crucial for mitochondrial quality control and cellular homeostasis.
- Transmissible gastroenteritis virus (TGEV) causes severe diarrhea in piglets, but its effect on mitophagy is unknown.
Purpose of the Study:
- To investigate the role of mitophagy in TGEV infection of porcine epithelial cells.
- To understand how TGEV impacts mitochondrial health and cellular responses.
Main Methods:
- Infection of porcine epithelial cells (IPEC-J2) with TGEV.
- Observation of mitochondrial morphology and mitophagy.
- Analysis of oxidative stress markers and apoptosis.
- Gene silencing of DJ-1 to assess its role.
Main Results:
- TGEV infection induced mitochondrial injury and mitophagy in IPEC-J2 cells.
- Mitophagy suppressed TGEV-induced oxidative stress and apoptosis.
- TGEV upregulated DJ-1 and antioxidant genes.
- Silencing DJ-1 inhibited mitophagy and increased apoptosis.
- TGEV nucleocapsid protein (N) was found in mitochondria and mitophagosomes.
Conclusions:
- TGEV infection activates mitophagy as a protective mechanism against oxidative stress and apoptosis.
- DJ-1 plays a role in mediating TGEV-induced mitophagy.
- The viral N protein localizes to mitochondria, suggesting a direct interaction.
- Mitophagy may promote cell survival and facilitate TGEV infection.
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