MAVS是RIG-I样受体介导的先天性免疫应答信号传导途径中唯一的接头分子，通过募集下游一系列E3连接酶，影响IFN-I的激活。病毒感染后，MAVS形成的高分子量多聚物对信号的传递和激活至关重要。因而，MAVS多聚物适时的移除对于信号的终止是必须的。虽然有多篇文章报道了MAVS的降解机制，但是MAVS多聚体的自噬降解尚无报道。我们前期研究发现，E3连接酶RNF34介导野生型MAVS的自噬降解，但不影响其多聚突变体的泛素化修饰和降解；RNF34缺陷的细胞，病毒感染诱导产生的MAVS聚集体显著增多，MAVS聚集体的清除显著滞后。初步研究结果显示，RNF34抑制RLRs信号通路的激活，促进病毒诱导产生的损伤线粒体的清除。本项目拟进一步研究MAVS多聚体降解机制、阐明RNF34对病毒感染诱发的线粒体自噬的调控作用，揭示干扰素信号通路和细胞选择性自噬信号通路之间的交互作用。

Viral infection triggers the formation of large mitochondrial antiviral signaling protein (MAVS) aggregates, which potently activate IRF3 and promote immune and inflammatory signaling. Previous studies have shown that autophagy has an important role in controlling MAVS-mediated antiviral signaling; however, the exact molecular mechanism underlying targeted autophagic degradation of MAVS aggregates remains unclear. Here, we investigated the mechanism by which RNF34, an E3 ubiquitin ligase, regulates immunity and mitophagy by inducing autophagic degradation of MAVS aggregates. A MAVS aggregation-deficient mutant, known as the MAVS-R64/65A, could not be degraded through the autophagy–lysosomal pathway. Notably, RNF34 negatively regulates RIG-I-like receptor (RLR) signaling pathways, and loss of RNF34 led to defective mitophagy. Based on these results, we would like to elucidate the mechanism by which RNF34-mediated ubiquitination of MAVS aggregates and its involvement in the innate immune response, mitochondrial homeostasis and infection.