Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization

Ferroptosis, a form of cell death instigated by iron-dependent lipid peroxidation reactions (LPO), is emerging as a promising therapeutic target for cancer. While the mechanisms governing LPO induction and suppression have gradually been unveiled, questions persist regarding the specific cellular location of LPO and the utilization of iron in driving cell death. A comprehensive understanding of these aspects holds significant potential for advancing therapeutic applications in disease management. Here, we show lysosomal LPO in the initiation of ferroptosis, leveraging the hidden abilities of fluorescent detection probes. Intra-lysosomal LPO triggers iron leakage, fostering cell-wide LPO by augmenting lysosomal…

• TS
  Takeda Science Foundation
• JA
  Japan Agency for Medical Research and Development

  Awards: CREST, JP22gm0910013
• JS
  Japan Society for the Promotion of Science

  Awards: 22H05572, 23H05481, CREST, 18K19405, 22KJ2465, 20H00493
• CR
  Core Research for Evolutional Science and Technology

  Award: JP22gm0910013