Apoptosis is an important cellular response to viral infection. In current study, we identified activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) as a positive regulator of apoptosis triggered by dsRNA. Depletion of AMBRA1 by gene editing significantly reduced dsRNA-induced apoptosis, which was largely restored by trans-complementation of AMBRA1. Mechanistically, AMBRA1 interacts with mitochondrial antiviral-signaling protein (MAVS), a key mitochondrial adaptor in the apoptosis pathway induced by dsRNA and viral infection. Further Co-IP analysis demonstrated that the mitochondrial localization of MAVS was essential for their interaction. The impact of AMBRA1 on dsRNA-induced apoptosis relied on the presence of MAVS and caspase-8. AMBRA1 was involved in the stabilization of MAVS through preventing its proteasomal degradation induced by dsRNA. Consistently, AMBRA1 upregulated the apoptosis induced by Semliki Forest virus infection. Taken together, our work illustrated a role of AMBRA1 in the virus-induced apoptosis through interacting with and stabilizing MAVS.
AMBRA1 promotes apoptosis induced by dsRNA and virus through interacting with and stabilizing MAVS
These authors contributed equally to this work.
- Award Group:
- Funder(s): National Natural Science Foundation of China
- Award Id(s): 31970887
- Funder(s):
- Award Group:
- Funder(s): Guangdong Provincial Applied Science and Technology Research and Development Program
- Award Id(s): 2018A050506029
- Funder(s):
- Award Group:
- Funder(s): Natural Science Foundation of Guangdong Province
- Award Id(s): 2020A1515010870
- Funder(s):
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Yuxia Lin, Changbai Huang, Huixin Gao, Xiaobo Li, Quanshi Lin, Shili Zhou, Zhiting Huo, Yanxia Huang, Chao Liu, Ping Zhang; AMBRA1 promotes apoptosis induced by dsRNA and virus through interacting with and stabilizing MAVS. J Cell Sci 2021; jcs.258910. doi: https://doi.org/10.1242/jcs.258910
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