AKAP1/PKA-mediated GRP75 phosphorylation at mitochondria-associated endoplasmic reticulum membranes protects cancer cells against ferroptosis.

ABSTRACT: Emerging evidence suggests that signaling pathways can be spatially regulated to ensure rapid and efficient responses to dynamically changing local cues. Ferroptosis is a recently defined form of lipid peroxidation-driven cell death. Although the molecular mechanisms underlying ferroptosis are emerging, spatial aspects of its signaling remain largely unexplored. By analyzing a public database, we found that a mitochondrial chaperone protein, glucose-regulated protein 75 (GRP75), may have a previously undefined role in regulating ferroptosis. This was subsequently validated. Interestingly, under ferroptotic conditions, GRP75 translocated from mitochondria to mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and the cytosol. Further mechanistic studies revealed a highly spa

SUBMITTER: Liu H 

PROVIDER: S-EPMC11893801 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature