DFCP1-containing ER microdomains mediate lysosomal membrane repair.

DFCP1 mediates lysosomal membrane repair by concentrating ER-associated lipid transport machinery at damaged lysosomes, crucial for cellular resistance to vacuolar damage.

• Why it matters: Maintaining lysosomal membrane integrity is vital for cellular homeostasis, yet the mechanisms regulating repair pathways and lipid transfer remain poorly understood, limiting potential therapeutic strategies.
• What they did: The study used molecular and cellular approaches to show that PI3P-enriched ER domains, formed by PIK3C3/VPS34, recruit DFCP1 via its PI3P-binding ability, facilitating lipid transfer and lysosomal sealing.
• The result: Findings reveal that DFCP1's ATPase activity is essential for its function, and its absence impairs lysosomal repair, highlighting its role in cellular defense mechanisms and potential targets for enhancing lysosomal stability.