Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization.

ABSTRACT: 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 membrane permeabilization (LMP). Conversely, cell lines with low susceptibility

SUBMITTER: Saimoto Y 

PROVIDER: S-EPMC11997074 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature