Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
06
11
2019
accepted:
01
06
2020
revised:
17
05
2020
pubmed:
8
7
2020
medline:
3
2
2022
entrez:
8
7
2020
Statut:
ppublish
Résumé
Mutations in pitrilysin metallopeptidase 1 (PITRM1), a mitochondrial protease involved in mitochondrial precursor processing and degradation, result in a slow-progressing syndrome characterized by cerebellar ataxia, psychotic episodes, and obsessive behavior, as well as cognitive decline. To investigate the pathogenetic mechanisms of mitochondrial presequence processing, we employed cortical neurons and cerebral organoids generated from PITRM1-knockout human induced pluripotent stem cells (iPSCs). PITRM1 deficiency strongly induced mitochondrial unfolded protein response (UPR
Identifiants
pubmed: 32632204
doi: 10.1038/s41380-020-0807-4
pii: 10.1038/s41380-020-0807-4
pmc: PMC8758476
mid: EMS135869
doi:
Substances chimiques
Amyloid beta-Peptides
0
Metalloendopeptidases
EC 3.4.24.-
PITRM1 protein, human
EC 3.4.24.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5733-5750Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/P007031/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1002/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00015/5
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-155-0001-S-MARTI
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-155-0005-RG-ZEVI-C0784
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-155-0002-RG-ZEVIA
Pays : United Kingdom
Informations de copyright
© 2020. The Author(s).
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