Glutaminolysis and transferrin regulate ferroptosis Journal Article
| Authors: | Gao, M.; Monian, P.; Quadri, N.; Ramasamy, R.; Jiang, X. |
| Article Title: | Glutaminolysis and transferrin regulate ferroptosis |
| 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 tobe ferroptosis. Two serum factors, the iron-carrier protein transferrin and amino acid glutamine, wereidentified 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. © 2015 Elsevier Inc. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; metabolism; apoptosis; necrosis; amino acid; nutrient; cell metabolism; glutamine; transferrin; heart injury; starvation; cell surface; reperfusion injury; transferrin receptor; aminolysis; glutaminolysis; ferroptosis; male; article; serum factor |
| Journal Title: | Molecular Cell |
| Volume: | 59 |
| Issue: | 2 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2015-07-16 |
| Start Page: | 298 |
| End Page: | 308 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2015.06.011 |
| PROVIDER: | scopus |
| PMCID: | PMC4506736 |
| PUBMED: | 26166707 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work