The Reduced Oligomerization of MAVS Mediated by ROS Enhances the Cellular Radioresistance

Abstract

Although the mitochondrial antiviral signaling protein (MAVS), located in the mitochondrial outmembrane, is believed to be a signaling adaptor with antiviral feature firstly, it has been shown that suppression of MAVS enhanced radioresistance. The mechanisms underlying this radioresistance remain unclear. Our current study demonstrated that knockdown of MAVS alleviated the radiation-induced mitochondrial dysfunction (mitochondrial membrane potential disruption and ATP production), downregulated the expressions of proapoptotic proteins, and reduced the generation of ROS in cells after irradiation. Furthermore, inhibition of mitochondrial ROS by the mitochondria-targeted antioxidant MitoQ reduced amounts of oligomerized MAVS after irradiation compared with the control group and also prevented the incidence of MN and increased the survival fraction of normal A549 cells after irradiation. To our knowledge, it is the first report to indicate that MAVS, an innate immune signaling molecule, is involved in radiation response via its oligomerization mediated by radiation-induced ROS, which may be a potential target for the precise radiotherapy or radioprotection.

WITHDRAWN: Dynamic Regulation of MAVS Protein Function via Reversible Oxidation at Cys79in Response to Oxidant Stimuli

“…Accumulating evidence lends strong support to the existence of a complex interplay between redox regulation and the interferon-mediated innate immune response. Notably, responses orchestrated by MAVS are subject to redox regulation by ROS originating from the NOX2 NADPH oxidase and mitochondria, although the specific mechanism remains to be fully deciphered [24][25][26][27]. The intriguing observation that oxidative stress alone, induced chemically either through glucose oxidase or MitoParaquat, holds the capability to trigger the assembly of functional MAVS aggregates [28] has spurred considerable interest in elucidating the underlying mechanisms and exploring the potential functional influence of Cys ox-PTMs.…”

Overexpression of the mitochondrial anti-viral signaling protein, MAVS, in cancers is associated with cell survival and inflammation

“…MAVS activates TBK1, which phosphorylates and promotes nuclear translocation of the IRF3/IRF7 transcription factor and, subsequently, the production of interferons and other associated inflammatory cytokines, such as IL-6 and IL-18. 19 , 71 …”

Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives

“…MAVS plays a role in the expression of IFN-β and IFN-stimulated genes in response to IR. MAVS complexes facilitate the nuclear translocation of the NF-κB and IRF3/7 transcription factors, consequently inducing the innate antiviral response [ 88 ].…”