The Production And Function Of ROS In Necroptosis

In tumor necrosis factor(TNF)-induced programmed cell necrosis,the receptorinteracting protein kinase(RIP3)regulates the production of reactive oxygen species ROS to promote this death process.It is known that RIP3 regulates the production of ROS through the catabolism of glutamine,but it is still not clear what protein is used to regulate it.Our study found that RIP3 can directly phosphorylate the T135 site of the E3 subunit(PDC-E3)in the pyruvate dehydrogenase complex.This process directly activates the pyruvate dehydrogenase complex PDC,which is glycolysis,a restriction enzyme during aerobic respiration.When PDC is activated,it can promote aerobic respiration and the subsequent electron transfer chain process,resulting in a large number of mitochondrial ROS production,and the resulting ROS can also promote programmed cell necrosis.Our work has found an important mechanism of RIP3 in regulating PDC.This process may be the main reason for the production of ROS in TNF-induced programmed necrosis.This result provides a new research basis for the study of pathological processes associated with cell necrosis and direction.