Annexin A7 mediates lysosome repair independently of ESCRT-III

  • Front Cell Dev Biol. 2024 Jan 23:11:1211498. doi: 10.3389/fcell.2023.1211498.
Malene Laage Ebstrup  #  1 ,  Stine Lauritzen Sønder  #  1 ,  Ditte Louise Fogde  2 ,  Anne Sofie Busk Heitmann  1 ,  Tiina Naumanen Dietrich  3 ,  Catarina Dias  1 ,  Marja Jäättelä  2  4 ,  Kenji Maeda  2 ,  Jesper Nylandsted  1  5
Affiliations
  • 1. Membrane Integrity, Danish Cancer Institute, Copenhagen, Denmark.
  • 2. Cell Death and Metabolism, Danish Cancer Institute, Copenhagen, Denmark.
  • 3. Bioimaging Core Facility, Danish Cancer Institute, Copenhagen, Denmark.
  • 4. Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 5. Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
  • # Contributed equally.
PMID: 38348092 DOI: 10.3389/fcell.2023.1211498
Abstract

Lysosomes are crucial organelles essential for various cellular processes, and any damage to them can severely compromise cell viability. This study uncovers a previously unrecognized function of the calcium- and phospholipid-binding protein Annexin A7 in lysosome repair, which operates independently of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. Our research reveals that Annexin A7 plays a role in repairing damaged lysosomes, different from its role in repairing the plasma membrane, where it facilitates repair through the recruitment of ESCRT-III components. Notably, our findings strongly suggest that Annexin A7, like the ESCRT machinery, is dispensable for membrane contact site formation within the newly discovered phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway. Instead, we speculate that Annexin A7 is recruited to damaged lysosomes and promotes repair through its membrane curvature and cross-linking capabilities. Our findings provide new insights into the diverse mechanisms underlying lysosomal membrane repair and highlight the multifunctional role of Annexin A7 in membrane repair.

Keywords
Annexin A7; ER-lysosome membrane contact sites (MCSs); L-Leucyl-L-Leucine O-methyl ester (LLOMe); endosomal sorting complexes required for transport III (ESCRT-III); lysosomal integrity; lysosomal membrane permeabilization; lysosome membrane repair; organelle repair.