Cell子刊：姜学军团队揭示铁死亡新路线

Core Viewpoint - The research reveals the critical role of endocytosis in cysteine-deprivation-induced ferroptosis, challenging previous understandings of lysosomal inhibitor mechanisms and suggesting different execution pathways for ferroptosis [3][7]. Group 1: Key Findings - Lysosomal inhibitors can independently suppress cysteine-deprivation-induced (CDI) ferroptosis, regardless of autophagy [5]. - Endocytosis is essential for CDI ferroptosis but is not required for ferroptosis induced by GPX4 depletion [5]. - Endocytic defects reduce intracellular iron levels and prevent CDI ferroptosis [5]. Group 2: Mechanisms and Implications - Transferrin's clathrin-mediated endocytosis (CME) is crucial for driving CDI ferroptosis [4][5]. - Inhibition of lysosomal proteolytic activity does not prevent ferroptosis, while disrupting endosomal acidification and removing endocytic protein AP2M1 can block ferroptosis [4]. - Supplementing iron through ammonium iron citrate, independent of endocytosis, can restore CDI ferroptosis in cells with endocytic defects [4].