MAVS integrates glucose metabolism and RIG-I-like receptor signaling

作者：Qiao-qiao He, Yu Huang, Longyu Nie, Sheng Ren, Gang Xu, Fei-Yan Deng, Zhikui Cheng, Qi Zuo, Lin Zhang, Huanhuan Cai, Qiming Wang, Xinghuan Wang, Hong Ren, Huan Yan, Ke Xu, Li Zhou, Mengji Lu, Zhibing Lu, Ying Zhu, Shi Liu · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-41028-9 · 被引用次数：58 · 研究领域：interferon and immune responses、Immune cells in cancer、Immune Response and Inflammation

MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling in mitochondria, peroxisomes, and mitochondria-associated ER membranes (MAMs). However, the role of MAVS in glucose metabolism and RLR signaling cross-regulation and how these signaling pathways are coordinated among these organelles have not been defined. This study reports that RLR action drives a switch from glycolysis to the pentose phosphate pathway (PPP) and the hexosamine biosynthesis pathway (HBP) through MAVS. We show that peroxisomal MAVS is responsible for glucose flux shift into PPP and type III interferon (IFN) expression, whereas MAMs-located MAVS is responsible for glucose flux shift into HBP and type I IFN expression. Mechanistically, peroxisomal MAVS interacts with G6PD and the MAVS signalosome forms at peroxisomes by recruiting TNF receptor-associated factor 6 (TRAF6) and interferon regulatory factor 1 (IRF1). By contrast, MAMs-located MAVS interact with glutamine-fructose-6-phosphate transaminase, and the MAVS signalosome forms at MAMs by recruiting TRAF6 and TRAF2. Our findings suggest that MAVS mediates the interaction of RLR signaling and glucose metabolism.