The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
10
07
2020
accepted:
05
02
2021
revised:
13
01
2021
pubmed:
6
3
2021
medline:
27
1
2022
entrez:
5
3
2021
Statut:
ppublish
Résumé
Dysfunctional mitochondria characterise Parkinson's Disease (PD). Uncovering etiological molecules, which harm the homeostasis of mitochondria in response to pathological cues, is therefore pivotal to inform early diagnosis and therapy in the condition, especially in its idiopathic forms. This study proposes the 18 kDa Translocator Protein (TSPO) to be one of those. Both in vitro and in vivo data show that neurotoxins, which phenotypically mimic PD, increase TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy. TSPO amplifies the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signalling, forming positive feedback, which represses the transcription factor EB (TFEB) and the controlled production of lysosomes. Finally, genetic variances in the transcriptome confirm that TSPO is required to alter the autophagy-lysosomal pathway during neurotoxicity.
Identifiants
pubmed: 33664474
doi: 10.1038/s41380-021-01050-z
pii: 10.1038/s41380-021-01050-z
pmc: PMC8505241
doi:
Substances chimiques
Receptors, GABA
0
TSPO protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2721-2739Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M010384/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N007042/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
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