Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal

Area of Science:

• Cell Biology
• Molecular Biology
• Immunology

Background:

• Endomembrane damage triggers cellular repair, including ESCRT-mediated membrane repair and autophagy.
• Previous research suggested these repair pathways function independently.

Purpose of the Study:

• To investigate the role of galectin-3 (Gal3) in coordinating cellular responses to lysosomal damage.
• To determine if Gal3 links ESCRT and autophagy pathways.

Main Methods:

• Utilized cell models of lysosomal damage.
• Assessed the requirement of Gal3 and ESCRT components (ALIX, CHMP4) for repair.
• Investigated Gal3's role in autophagy and lysosomal replacement via TFEB.

Main Results:

• Gal3 is essential for recruiting ESCRT component ALIX to sites of lysosomal damage.
• Gal3 facilitates interactions between ALIX and CHMP4, crucial for lysosomal repair.
• Gal3 regulates autophagy following lysosomal injury; its absence activates TFEB-mediated lysosomal replacement.
• This coordinated response was observed in models of tauopathy and Mycobacterium tuberculosis infection.

Conclusions:

• Galectin-3 acts as a central coordinator of cellular homeostasis following lysosomal damage.
• Gal3 unifies ESCRT-dependent membrane repair and autophagy for efficient organelle quality control.
• The findings reveal a multi-stage repair process involving repair, removal, and replacement.