Molecular Cell
Volume 59, Issue 2, 16 July 2015, Pages 298-308
Journal home page for Molecular Cell

Article
Glutaminolysis and Transferrin Regulate Ferroptosis

https://doi.org/10.1016/j.molcel.2015.06.011Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Transferrin and glutamine are essential for the induction of ferroptotic cell death

  • Transferrin import is required for ferroptosis

  • The cellular metabolic process glutaminolysis is essential for ferroptosis

  • Inhibiting glutaminolysis reduces ischemia/reperfusion-induced heart injury ex vivo

Summary

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.

Cited by (0)