Oxidized phosphatidylinositol impairs lysosomal membrane repair to promote ferroptosis

Metabolic alterations and redox homeostasis in ferroptosis: emerging mechanisms and therapeutic implications

This review focuses on recent findings of perturbed metabolic processes in cancer that create a high iron demand and an altered lipid composition, thereby predisposing cells to ferroptosis and the therapeutic potential of pharmacological agents that can selectively trigger ferroptosis in tumor cells.

The subcellular landscape of ferroptosis: A cellular organelle perspective

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation. Its execution depends not only on the amount of lipid peroxides, but also on where oxidizable lipids, redox-active iron, reactive oxygen species, and antioxidant defenses are distributed within cells. This review summarizes curre...

Mitochondria-targeted tetraoxanes initiate lipid peroxidation to drive ferroptosis and tumor suppression.

Ferroptosis is implicated as a vulnerability in multiple cancers, yet approaches for effectively inducing ferroptosis in vivo are limited. Bypassing conventional strategies targeting the antiferroptotic glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins, we designed metabolic initiator...

Enzymatic Lipid Oxygenation and Ferroptosis Resistance: A Critical Evaluation of the Lipid Antioxidant Barrier Hypothesis

This review synthesizes the emerging paradigm of directed lipid oxygenation as a regulated, adaptive mechanism that may function as a physiologically regulated lipid antioxidant barrier for ferroptosis, and examines how enzymatic lipid oxygenation generates bioactive oxylipins that activate cytoprotective transcription...

Mitochondrial fission factor senses and governs ferroptosis

Calcium licenses lipid droplets for ferroptosis: A PKCβ-ACSL4-ALOX15 phosphorylation relay.

Ferroptosis is executed by iron-dependent phospholipid peroxidation, yet the upstream signals that determine when oxidizable lipid pools become lethal remain incompletely resolved. Recent work identifies a calcium-dependent protein kinase C beta (PKCβ) pathway that phosphorylates acyl-CoA synthetase long-chain family m...