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. Author manuscript; available in PMC: 2021 Mar 10.
Published in final edited form as: Trends Endocrinol Metab. 2019 Jul 23;30(9):571–573. doi: 10.1016/j.tem.2019.07.010

Figure 1: Model depicting lactate-mediated regulation of type I IFN production.

Figure 1:

(A) Under normal physiological conditions, HK-2 is localized on mitochondria partly through interacting with MAVS and catalyzes the conversion of glucose to glucose-6-P, which is subsequently converted to pyruvate through a series of glycolytic reactions. Pyruvate can either be shunted into the TCA cycle in mitochondria or converted to lactate by LDHA. Lactate binds to MAVS and inhibits downstream RLR signaling. (B) Upon viral infection, viral RNAs promote the RIG-I-MAVS interaction and displace HK-2 from mitochondria, resulting in decreased glycolytic flux and reduced lactate production. This subsequently relieves MAVS from its lactate-mediated inhibition, leading to the activation of downstream RLR signaling and IRF3-mediated type I IFN production. The grey color in gene names or arrows indicates inactivation of corresponding proteins or suppression of corresponding pathways. HK-2: hexokinase 2; MAVS: mitochondrial antiviral-signaling; Glucose-6-P: Glucose-6-phosphate; RIG-I: retinoic-acid-inducible gene I; TBK1: TANK binding kinase 1; IRF3: interferon regulatory factor 3; IFN: interferon; LDHA: lactate dehydrogenase; TCA: tricarboxylic acid.