Lysosomal quality control Review

2025/02/19 by Danielle Henn, Xi Yang, Ming Li · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Calcium signaling and nucleotide metabolism #Lysosomal Storage Disorders Research #Retinal Diseases and Treatments

paper · pdf · doi:10.1080/15548627.2025.2469206

openalex publication_date 2025/02/19 · openalex created_date 2025/02/20 · openalex updated_date 2026/08/01

Abstract

Healthy cells need functional lysosomes to degrade cargo delivered by autophagy and endocytosis. Defective lysosomes can lead to severe conditions such as lysosomal storage diseases (LSDs) and neurodegeneration. To maintain lysosome integrity and functionality, cells have evolved multiple quality control pathways corresponding to different types of stress and damage. These can be divided into five levels: regulation, reformation, repair, removal, and replacement. The different levels of lysosome quality control often work together to maintain the integrity of the lysosomal network. This review summarizes the different quality control pathways and discusses the less-studied area of lysosome membrane protein regulation and degradation, highlighting key unanswered questions in the field.

Citations

• Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation
• Lysosomal membrane permeabilization in cell death
• Ubiquitination of exposed glycoproteins by SCF FBXO27 directs damaged lysosomes for autophagy
• G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules
• SMART: recent updates, new developments and status in 2020
• Annexins A1 and A2 are recruited to larger lysosomal injuries independently of ESCRTs to promote repair
• Proceedings of the National Academy of Sciences
• Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy

Discussions

• How do cells maintain lysosomal integrity under stress? In our latest review, we break down five levels of lysosomal quality control—regulation, reformation, repair, removal, and replacement. Summariz [bsky, 0 points, 0 comments]

Related

• Lysosomal Physiology
• Lysosomal storage disorders: The cellular impact of lysosomal dysfunction
• Lysosomal homeostasis at the crossroads of neurodegeneration
• Repair condensates and lipid domains in lysosome integrity
• Lysosome signaling in cell survival and programmed cell death for cellular homeostasis