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Annexin A7 mediates lysosome repair independently of ESCRT-III.

Frontiers in cell and developmental biology (2024-02-13)
Malene Laage Ebstrup, Stine Lauritzen Sønder, Ditte Louise Fogde, Anne Sofie Busk Heitmann, Tiina Naumanen Dietrich, Catarina Dias, Marja Jäättelä, Kenji Maeda, Jesper Nylandsted
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.

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