Format:
Online-Ressource
ISSN:
1469-3178
Content:
Abstract: Lysosomes are degradative organelles and signaling hubs that maintain cell and tissue homeostasis, and lysosomal dysfunction is implicated in aging and reduced longevity. Lysosomes are frequently damaged, but their repair mechanisms remain unclear. Here, we demonstrate that damaged lysosomal membranes are repaired by microautophagy (a process termed “microlysophagy”) and identify key regulators of the first and last steps. We reveal the AGC kinase STK38 as a novel microlysophagy regulator. Through phosphorylation of the scaffold protein DOK1, STK38 is specifically required for the lysosomal recruitment of the AAA+ ATPase VPS4, which terminates microlysophagy by promoting the disassembly of ESCRT components. By contrast, microlysophagy initiation involves non‐canonical lipidation of ATG8s, especially the GABARAP subfamily, which is required for ESCRT assembly through interaction with ALIX. Depletion of STK38 and GABARAPs accelerates DNA damage‐induced cellular senescence in human cells and curtails lifespan in C. elegans, respectively. Thus, microlysophagy is regulated by STK38 and GABARAPs and could be essential for maintaining lysosomal integrity and preventing aging.
In:
day:21
In:
month:11
In:
year:2023
In:
extent:28
In:
European Molecular Biology Organization, EMBO reports, Heidelberg : EMBO Press, [200]-, (21.11.2023) (gesamt 28), 1469-3178
Language:
English
DOI:
10.15252/embr.202357300
URN:
urn:nbn:de:101:1-2023112115143860624001
URL:
https://doi.org/10.15252/embr.202357300
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023112115143860624001
URL:
https://d-nb.info/1310677948/34
URL:
https://doi.org/10.15252/embr.202357300
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