The mitochondrial protein ERAL1 suppresses RNA virus infection by facilitating RIG-I-like receptor signaling

• DOI: 10.1016/j.celrep.2020.108631
• Publication Date: 2021-01-19T15:38:23Z
• Authors: Siji Li; Ming Kuang; Luoying Chen; Yunfei Li; Shengde Liu; Hongqiang Du; Lili Cao; Fuping You
• Keywords: 0301 basic medicine; RNA-Binding Proteins; 3. Good health; Mice, Inbred C57BL; Mitochondrial Proteins; Mice; 03 medical and health sciences; HEK293 Cells; RNA Virus Infections; GTP-Binding Proteins; Animals; DEAD Box Protein 58; Humans; Receptors, Immunologic; HeLa Cells; Signal Transduction

Mitochondria not only serve as a platform for innate immune signaling transduction but also enhance immune responses by releasing mitochondrial DNA and RNA into the cytoplasm. However, whether mitochondrial matrix proteins could be liberated and involved in immune responses remains enigmatic. Here, we identify the mitochondrial protein ERA G-protein-like 1 (ERAL1) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein by using proximity-based labeling technology. ERAL1 deficiency markedly reduces the downstream antiviral signaling triggered by RNA viruses. Moreover, ERAL1-deficient mice are more susceptible to lethality following RNA virus infection than wild-type mice. After virus infection, ERAL1 is released from mitochondria through the BAX/BAK pore. The cytosolic ERAL1 facilitates lysine 63 (K63)-linked ubiquitination of retinoicacid inducible gene-1 (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) and promotes downstream MAVS polymerization, thus positively regulating antiviral responses.