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Mol Cell. 2015 Jul 16;59(2):298-308. doi: 10.1016/j.molcel.2015.06.011. Epub 2015 Jul 9.

Glutaminolysis and Transferrin Regulate Ferroptosis.

Author information

1
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
2
Department of Medicine, Langone Medical Center, New York University, 522 1(st) Avenue, New York, NY 10016, USA.
3
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: jiangx@mskcc.org.

Abstract

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.

PMID:
26166707
PMCID:
PMC4506736
DOI:
10.1016/j.molcel.2015.06.011
[Indexed for MEDLINE]
Free PMC Article

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