Annexin A7 mediates lysosome repair independently of ESCRT-III

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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.

OriginalsprogEngelsk
Artikelnummer1211498
TidsskriftFrontiers in Cell and Developmental Biology
Vol/bind11
Antal sider19
ISSN2296-634X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was supported by the Scientific Committee Danish Cancer Society (R90-A5847-14-S2, R269-A15812), the Danish Council for Independent Research (6108-00378A, 9040-00252B), and the Novo Nordisk Foundation (NNF18OC0034936).

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Copyright © 2024 Ebstrup, Sønder, Fogde, Heitmann, Dietrich, Dias, Jäättelä, Maeda and Nylandsted.

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