Titre
Early onset effects of single substrate accumulation recapitulate major features of LSD in patient-derived lysosomes.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Scerra, G.
Auteure/Auteur
De Pasquale, V.
Auteure/Auteur
Pavone, L.M.
Auteure/Auteur
Caporaso, M.G.
Auteure/Auteur
Mayer, A.
Auteure/Auteur
Renna, M.
Auteure/Auteur
D'Agostino, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2589-0042
Statut éditorial
Publié
Date de publication
2021-07-23
Volume
24
Numéro
7
Première page
102707
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Lysosome functions mainly rely on their ability to either degrade substrates or release them into the extracellular space. Lysosomal storage disorders (LSDs) are commonly characterized by a chronic lysosomal accumulation of different substrates, thereby causing lysosomal dysfunctions and secretion defects. However, the early effects of substrate accumulation on lysosomal homeostasis have not been analyzed so far. Here, we describe how the acute accumulation of a single substrate determines a rapid centripetal redistribution of the lysosomes, triggering their expansion and reducing their secretion, by limiting the motility of these organelles toward the plasma membrane. Moreover, we provide evidence that such defects could be explained by a trapping mechanism exerted by the extensive contacts between the enlarged lysosomes and the highly intertwined membrane structures of the endoplasmic reticulum which might represent a crucial biological cue ultimately leading to the clinically relevant secondary defects observed in the LSD experimental models and patients.
PID Serval
serval:BIB_1BF329C273C5
PMID
Open Access
Oui
Date de création
2021-07-15T12:07:53.345Z
Date de création dans IRIS
2025-05-20T16:43:35Z
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Nom
iScience 2021 Scerra copy.pdf
Version du manuscrit
published
Taille
5.5 MB
Format
Adobe PDF
PID Serval
serval:BIB_1BF329C273C5.P001
URN
urn:nbn:ch:serval-BIB_1BF329C273C53
Somme de contrôle
(MD5):657b66f8e88ac408412cb8885d36525d