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

Qiao-qiao He, Yu Huang, Longyu Nie, Sheng Ren, Gang Xu, Feiyan Deng, Zhikui Cheng, Qi Zuo, Lin Zhang, Huanhuan Cai, Qiming Wang, Fubing Wang, Hong Ren, Huan Yan, Ke Xu, Li Zhou, Mengji Lu, Zhibing Lu, Ying Zhu () and Shi Liu ()
Additional contact information
Qiao-qiao He: Wuhan University
Yu Huang: Wuhan University
Longyu Nie: Wuhan University
Sheng Ren: Wuhan University
Gang Xu: Wuhan University
Feiyan Deng: Wuhan University
Zhikui Cheng: Wuhan University
Qi Zuo: Wuhan University
Lin Zhang: Wuhan University
Huanhuan Cai: Wuhan University
Qiming Wang: Hunan Agricultural University
Fubing Wang: Chinese Academy of Medical Sciences
Hong Ren: Affiliated Hospital to Shanghai Jiao Tong University School of Medicine
Huan Yan: Wuhan University
Ke Xu: Wuhan University
Li Zhou: Wuhan University
Mengji Lu: University Hospital Essen, University of Duisburg-Essen
Zhibing Lu: Wuhan University
Ying Zhu: Wuhan University
Shi Liu: Wuhan University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-41028-9

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