Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species

We identified a p53 target gene, phosphate-activated mitochondrial glutaminase (GLS2), a key enzyme in conversion of glutamine to glutamate, and thereby a regulator of glutathione (GSH) synthesis and energy production. GLS2 expression is induced in response to DNA damage or oxidative stress in a p53-dependent manner, and p53 associates with the GLS2 promoter. Elevated GLS2 facilitates glutamine metabolism and lowers intracellular reactive oxygen species (ROS) levels, resulting in an overall decrease in DNA oxidation as determined by measurement of 8-OH-dG content in both normal and stressed cells. Further, siRNA down-regulation of either GLS2 or p53 compromises the GSH-dependent antioxidant system and…

• TS
  Takeda Science Foundation
• SF
  Sumitomo Foundation
• TB
  Tokyo Biochemical Research Foundation
• MO
  Ministry of Education, Culture, Sports, Science and Technology

  Awards: 21390147, 17016010, 19659121
• JD
  Japan Diabetes Foundation
• NI
  National Institutes of Health

  Award: CA87497