18.03.2024 - 15:51:06

Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH

The latest paper by Pinki Gahlot from the Meyer lab (A03), published in Molecular Cell, reveals how human cells detect and respond to lipid bilayer disruptions in compromised lysosomes, leading to lysophagy via ubiquitin-triggered pathways instead of membrane repair. SPG20, binding to the repair factor IST1, detects damage-associated lipid-packing defects before membrane rupture. These extensive defects lead SPG20 to recruit and activate ITCH, initiating lysophagy to eliminate the damaged lysosome. These findings underscore the importance of coordinated lysosomal damage responses for maintaining cellular homeostasis.