Oxidative stress induces mitochondrial iron overload and ferroptotic cell death

Abstract Oxidative stress has been shown to induce cell death in a wide range of human diseases including cardiac ischemia/reperfusion injury, drug induced cardiotoxicity, and heart failure. However, the mechanism of cell death induced by oxidative stress remains incompletely understood. Here we provide new evidence that oxidative stress primarily induces ferroptosis, but not apoptosis, necroptosis, or mitochondria-mediated necrosis, in cardiomyocytes. Intriguingly, oxidative stress induced by organic oxidants such as tert-butyl hydroperoxide (tBHP) and cumene hydroperoxide (CHP), but not hydrogen peroxide (H 2 O 2 ), promoted glutathione depletion and glutathione peroxidase 4 (GPX4) degradation in…

• AH
  American Heart Association

  Award: 19TPA34850148
• UO
  University of Washington
• NI
  National Institutes of Health

  Awards: R01HL160767, R01HL155035, R01HL160767 and R01HL155035