Molecular cell

Cell intake process is needed for cell death caused by cysteine loss

Updated

Abstract

Lysosomal inhibitors suppress cysteine-deprivation-induced ferroptosis even in autophagy-defective cells.

  • Ferroptosis is linked to the breakdown of iron-dependent lipids, leading to cell death.
  • Autophagic degradation of ferritin increases bioactive iron, which may promote ferroptosis.
  • Clathrin-mediated endocytosis of transferrin is necessary for cysteine-deprivation-induced ferroptosis.
  • Blocking endosomal acidification and the endocytic protein AP2M1 disrupts ferroptosis.
  • Restoring cellular iron with ferric ammonium citrate can reinstate ferroptosis in cells lacking endocytosis.
  • Direct inhibition of the enzyme glutathione peroxidase-4 does not require endocytosis or increased cellular iron to trigger ferroptosis.

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Full Text

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Funding

Competing interests

Declaration of interests X.J. and D.L. are inventors on patents related to autophagy and cell death. X.J. holds equity in, and consults for, Exarta Therapeutics and Lime Therapeutics.
PubMed

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