ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
03
07
2020
accepted:
17
03
2021
revised:
16
03
2021
pubmed:
3
4
2021
medline:
22
3
2022
entrez:
2
4
2021
Statut:
ppublish
Résumé
Despite the great advances in autophagy research in the last years, the specific functions of the four mammalian Atg4 proteases (ATG4A-D) remain unclear. In yeast, Atg4 mediates both Atg8 proteolytic activation, and its delipidation. However, it is not clear how these two roles are distributed along the members of the ATG4 family of proteases. We show that these two functions are preferentially carried out by distinct ATG4 proteases, being ATG4D the main delipidating enzyme. In mammalian cells, ATG4D loss results in accumulation of membrane-bound forms of mATG8s, increased cellular autophagosome number and reduced autophagosome average size. In mice, ATG4D loss leads to cerebellar neurodegeneration and impaired motor coordination caused by alterations in trafficking/clustering of GABA
Identifiants
pubmed: 33795848
doi: 10.1038/s41418-021-00776-1
pii: 10.1038/s41418-021-00776-1
pmc: PMC8408152
doi:
Substances chimiques
Autophagy-Related Protein 8 Family
0
Autophagy-Related Proteins
0
ATG4D protein, human
EC 3.4.22.-
Cysteine Endopeptidases
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2651-2672Subventions
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : BFU2015-68539-R
Organisme : Gobierno del Principado de Asturias (Government of the Principality of Asturias)
ID : IDI/2018/000159
Commentaires et corrections
Type : ErratumIn
Type : CommentIn
Informations de copyright
© 2021. The Author(s).
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