Migratory autolysosome disposal mitigates lysosome damage

J Cell Biol. 2024 Dec 2;223(12):e202403195. doi: 10.1083/jcb.202403195. Epub 2024 Sep 30.

Abstract

Lysosomes, essential for intracellular degradation and recycling, employ damage-control strategies such as lysophagy and membrane repair mechanisms to maintain functionality and cellular homeostasis. Our study unveils migratory autolysosome disposal (MAD), a response to lysosomal damage where cells expel LAMP1-LC3 positive structures via autolysosome exocytosis, requiring autophagy machinery, SNARE proteins, and cell migration. This mechanism, crucial for mitigating lysosomal damage, underscores the role of cell migration in lysosome damage control and facilitates the release of small extracellular vesicles, highlighting the intricate relationship between cell migration, organelle quality control, and extracellular vesicle release.

MeSH terms

  • Animals
  • Autophagy*
  • Cell Movement*
  • Exocytosis
  • Extracellular Vesicles / metabolism
  • HeLa Cells
  • Humans
  • Lysosomal Membrane Proteins / genetics
  • Lysosomal Membrane Proteins / metabolism
  • Lysosomal-Associated Membrane Protein 1
  • Lysosomes* / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism

Substances

  • Microtubule-Associated Proteins
  • SNARE Proteins
  • Lysosomal Membrane Proteins
  • MAP1LC3A protein, human
  • LAMP1 protein, human
  • Lysosomal-Associated Membrane Protein 1