Glutaminolysis and Transferrin Regulate Ferroptosis

被引:1797
作者
Gao, Minghui [1 ]
Monian, Prashant [1 ]
Quadri, Nosirudeen [2 ]
Ramasamy, Ravichandran [2 ]
Jiang, Xuejun [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA
[2] NYU, Langone Med Ctr, Dept Med, New York, NY 10016 USA
关键词
CELL-DEATH; GLUTAMINASE ACTIVITY; MOLECULAR SWITCH; RIP3; GLUTATHIONE; NECROSIS; KINASE; CANCER; IDENTIFICATION; NECROPTOSIS;
D O I
10.1016/j.molcel.2015.06.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ferroptosis has emerged as a new form of regulated necrosis that is implicated in various human diseases. However, the mechanisms of ferroptosis are not well defined. This study reports the discovery of multiple molecular components of ferroptosis and its intimate interplay with cellular metabolism and redox machinery. Nutrient starvation often leads to sporadic apoptosis. Strikingly, we found that upon deprivation of amino acids, a more rapid and potent necrosis process can be induced in a serum-dependent manner, which was subsequently determined to be ferroptosis. Two serum factors, the iron-carrier protein transferrin and amino acid glutamine, were identified as the inducers of ferroptosis. We further found that the cell surface transferrin receptor and the glutamine-fueled intracellular metabolic pathway, glutaminolysis, played crucial roles in the death process. Inhibition of glutaminolysis, the essential component of ferroptosis, can reduce heart injury triggered by ischemia/reperfusion, suggesting a potential therapeutic approach for treating related diseases.
引用
收藏
页码:298 / 308
页数:11
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