TY - JOUR
T1 - The Reduced Oligomerization of MAVS Mediated by ROS Enhances the Cellular Radioresistance
AU - Du, Yarong
AU - Pan, Dong
AU - Jia, Rong
AU - Chen, Yaxiong
AU - Jia, Cong
AU - Wang, Jufang
AU - Hu, Burong
AU - Martin, Pamela M.
N1 - Funding Information:
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. Science and Technology Research Project of Gansu Province 17JR5RA307 145RTSA012 National Key Research and Development Program of China 2017YFC0108605 National Natural Science Foundation of China U1632145 11705248 11635013
Publisher Copyright:
© 2020 Yarong Du et al.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85082088348&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082088348&partnerID=8YFLogxK
U2 - 10.1155/2020/2167129
DO - 10.1155/2020/2167129
M3 - Article
C2 - 32190169
AN - SCOPUS:85082088348
SN - 1942-0900
VL - 2020
JO - Oxidative medicine and cellular longevity
JF - Oxidative medicine and cellular longevity
M1 - 2167129
ER -