Annexin A7 mediates lysosome repair independently of ESCRT-III

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 independentl...

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Main Authors: Malene Laage Ebstrup, Stine Lauritzen Sønder, Ditte Louise Fogde, Anne Sofie Busk Heitmann, Tiina Naumanen Dietrich, Catarina Dias, Marja Jäättelä, Kenji Maeda, Jesper Nylandsted
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1211498/full
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author Malene Laage Ebstrup
Stine Lauritzen Sønder
Ditte Louise Fogde
Anne Sofie Busk Heitmann
Tiina Naumanen Dietrich
Catarina Dias
Marja Jäättelä
Marja Jäättelä
Kenji Maeda
Jesper Nylandsted
Jesper Nylandsted
author_facet Malene Laage Ebstrup
Stine Lauritzen Sønder
Ditte Louise Fogde
Anne Sofie Busk Heitmann
Tiina Naumanen Dietrich
Catarina Dias
Marja Jäättelä
Marja Jäättelä
Kenji Maeda
Jesper Nylandsted
Jesper Nylandsted
author_sort Malene Laage Ebstrup
collection DOAJ
description 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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spelling doaj.art-bd1103947a9b433d9ba7b5a9098218ad2024-02-08T15:36:10ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-01-011110.3389/fcell.2023.12114981211498Annexin A7 mediates lysosome repair independently of ESCRT-IIIMalene Laage Ebstrup0Stine Lauritzen Sønder1Ditte Louise Fogde2Anne Sofie Busk Heitmann3Tiina Naumanen Dietrich4Catarina Dias5Marja Jäättelä6Marja Jäättelä7Kenji Maeda8Jesper Nylandsted9Jesper Nylandsted10Membrane Integrity, Danish Cancer Institute, Copenhagen, DenmarkMembrane Integrity, Danish Cancer Institute, Copenhagen, DenmarkCell Death and Metabolism, Danish Cancer Institute, Copenhagen, DenmarkMembrane Integrity, Danish Cancer Institute, Copenhagen, DenmarkBioimaging Core Facility, Danish Cancer Institute, Copenhagen, DenmarkMembrane Integrity, Danish Cancer Institute, Copenhagen, DenmarkCell Death and Metabolism, Danish Cancer Institute, Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkCell Death and Metabolism, Danish Cancer Institute, Copenhagen, DenmarkMembrane Integrity, Danish Cancer Institute, Copenhagen, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkLysosomes 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1211498/fulllysosome membrane repairlysosomal integritylysosomal membrane permeabilizationAnnexin A7endosomal sorting complexes required for transport III (ESCRT-III)L-Leucyl-L-Leucine O-methyl ester (LLOMe)
spellingShingle Malene Laage Ebstrup
Stine Lauritzen Sønder
Ditte Louise Fogde
Anne Sofie Busk Heitmann
Tiina Naumanen Dietrich
Catarina Dias
Marja Jäättelä
Marja Jäättelä
Kenji Maeda
Jesper Nylandsted
Jesper Nylandsted
Annexin A7 mediates lysosome repair independently of ESCRT-III
Frontiers in Cell and Developmental Biology
lysosome membrane repair
lysosomal integrity
lysosomal membrane permeabilization
Annexin A7
endosomal sorting complexes required for transport III (ESCRT-III)
L-Leucyl-L-Leucine O-methyl ester (LLOMe)
title Annexin A7 mediates lysosome repair independently of ESCRT-III
title_full Annexin A7 mediates lysosome repair independently of ESCRT-III
title_fullStr Annexin A7 mediates lysosome repair independently of ESCRT-III
title_full_unstemmed Annexin A7 mediates lysosome repair independently of ESCRT-III
title_short Annexin A7 mediates lysosome repair independently of ESCRT-III
title_sort annexin a7 mediates lysosome repair independently of escrt iii
topic lysosome membrane repair
lysosomal integrity
lysosomal membrane permeabilization
Annexin A7
endosomal sorting complexes required for transport III (ESCRT-III)
L-Leucyl-L-Leucine O-methyl ester (LLOMe)
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1211498/full
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