GCLC公司
半胱氨酸
胱氨酸
DNA连接酶
谷胱甘肽
细胞生物学
GCLM公司
谷氨酸受体
平衡
生物化学
生物
程序性细胞死亡
化学
酶
受体
细胞凋亡
作者
Yun Pyo Kang,Andrea Mockabee‐Macias,Chang Jiang,Aimee Falzone,Nicolas Prieto-Farigua,Everett Stone,Isaac S. Harris,Gina M. DeNicola
出处
期刊:Cell Metabolism
[Elsevier]
日期:2020-12-22
卷期号:33 (1): 174-189.e7
被引量:202
标识
DOI:10.1016/j.cmet.2020.12.007
摘要
Cysteine is required for maintaining cellular redox homeostasis in both normal and transformed cells. Deprivation of cysteine induces the iron-dependent form of cell death known as ferroptosis; however, the metabolic consequences of cysteine starvation beyond impairment of glutathione synthesis are poorly characterized. Here, we find that cystine starvation of non-small-cell lung cancer cell lines induces an unexpected accumulation of γ-glutamyl-peptides, which are produced due to a non-canonical activity of glutamate-cysteine ligase catalytic subunit (GCLC). This activity is enriched in cell lines with high levels of NRF2, a key transcriptional regulator of GCLC, but is also inducible in healthy murine tissues following cysteine limitation. γ-glutamyl-peptide synthesis limits the accumulation of glutamate, thereby protecting against ferroptosis. These results indicate that GCLC has a glutathione-independent, non-canonical role in the protection against ferroptosis by maintaining glutamate homeostasis under cystine starvation.
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