TY - JOUR

T1 - Annexin A7 mediates lysosome repair independently of ESCRT-III

AU - Ebstrup, Malene Laage

AU - Sønder, Stine Lauritzen

AU - Fogde, Ditte Louise

AU - Heitmann, Anne Sofie Busk

AU - Dietrich, Tiina Naumanen

AU - Dias, Catarina

AU - Jäättelä, Marja

AU - Maeda, Kenji

AU - Nylandsted, Jesper

N1 - Publisher Copyright: Copyright © 2024 Ebstrup, Sønder, Fogde, Heitmann, Dietrich, Dias, Jäättelä, Maeda and Nylandsted.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Annexin A7

KW - endosomal sorting complexes required for transport III (ESCRT-III)

KW - ER-lysosome membrane contact sites (MCSs)

KW - L-Leucyl-L-Leucine O-methyl ester (LLOMe)

KW - lysosomal integrity

KW - lysosomal membrane permeabilization

KW - lysosome membrane repair

KW - organelle repair

U2 - 10.3389/fcell.2023.1211498

DO - 10.3389/fcell.2023.1211498

M3 - Journal article

C2 - 38348092

AN - SCOPUS:85184239642

VL - 11

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

M1 - 1211498

ER -