RNF34 functions in immunity and selective mitophagy by targeting MAVS for autophagic degradation

• Xiang He ^[2] ; Yongjie Zhu ^[2] ; Yanhong Zhang ^[2] ; Yunqi Geng ^[3] ; Jing Gong ^[3] ; Jin Geng ^[3] ; Pingping Zhang ^[2] ; Xiaotong Zhang ^[2] ; Ning Liu ^[2] ; Yumeng Peng ^[2] ; Chenbin Wang ^[2] ; Yujie Wang ^[3] ; Xin Liu ^[2] ; Luming Wan ^[1] ; Feng Gong ^[1] ; Congwen Wei ^[2] ; Hui Zhong ^[2]
  1. [1] Academy of Military Medical Sciences

     Academy of Military Medical Sciences

     China

     
  2. [2] 1 Beijing Institute of Biotechnology Beijing China
  3. [3] 1 Beijing Institute of Biotechnology Beijing China; 2 Institute of Physical Science and Information Technology Anhui University Hefei China

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 14, 2019
• Idioma: inglés
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  • Viral infection triggers the formation of mitochondrial antiviral signaling protein (MAVS) aggregates, which potently promote immune signaling. Autophagy plays an important role in controlling MAVS‐mediated antiviral signaling; however, the exact molecular mechanism underlying the targeted autophagic degradation of MAVS remains unclear. Here, we investigated the mechanism by which RNF34 regulates immunity and mitophagy by targeting MAVS. RNF34 binds to MAVS in the mitochondrial compartment after viral infection and negatively regulates RIG‐I‐like receptor (RLR)‐mediated antiviral immunity. Moreover, RNF34 catalyzes the K27‐/K29‐linked ubiquitination of MAVS at Lys 297, 311, 348, and 362 Arg, which serves as a recognition signal for NDP52‐dependent autophagic degradation. Specifically, RNF34 initiates the K63‐ to K27‐linked ubiquitination transition on MAVS primarily at Lys 311, which facilitates the autophagic degradation of MAVS upon RIG‐I stimulation. Notably, RNF34 is required for the clearance of damaged mitochondria upon viral infection. Thus, we elucidated the mechanism by which RNF34‐mediated autophagic degradation of MAVS regulates the innate immune response, mitochondrial homeostasis, and infection.