TY - JOUR
T1 - Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation
AU - Lian, Gaojian
AU - Gnanaprakasam, J. N.Rashida
AU - Wang, Tingting
AU - Wu, Ruohan
AU - Chen, Xuyong
AU - Liu, Lingling
AU - Shen, Yuqing
AU - Yang, Mao
AU - Yang, Jun
AU - Chen, Ying
AU - Vasiliou, Vasilis
AU - Cassel, Teresa A.
AU - Green, Douglas R.
AU - Liu, Yusen
AU - Fan, Teresa W.M.
AU - Wang, Ruoning
N1 - Publisher Copyright:
© Lian et al.
PY - 2018/9
Y1 - 2018/9
N2 - Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate–cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis dampened the pathological progression of experimental autoimmune encephalomyelitis (EAE). We further reveal that glutamine provides essential precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism fuels de novo synthesis of GSH and directs the lineage choice in T cells.
AB - Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate–cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis dampened the pathological progression of experimental autoimmune encephalomyelitis (EAE). We further reveal that glutamine provides essential precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism fuels de novo synthesis of GSH and directs the lineage choice in T cells.
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U2 - 10.7554/eLife.36158
DO - 10.7554/eLife.36158
M3 - Article
C2 - 30198844
AN - SCOPUS:85058401910
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e36158
ER -