Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 01 2023
02 01 2023
Historique:
received:
09
03
2022
revised:
19
08
2022
accepted:
07
10
2022
entrez:
16
11
2022
pubmed:
17
11
2022
medline:
19
11
2022
Statut:
ppublish
Résumé
Astrocytes, often considered as secondary responders to neurodegeneration, are emerging as primary drivers of brain disease. Here we show that mitochondrial DNA depletion in astrocytes affects their primary cilium, the signaling organelle of a cell. The progressive oxidative phosphorylation deficiency in astrocytes induces FOXJ1 and RFX transcription factors, known as master regulators of motile ciliogenesis. Consequently, a robust gene expression program involving motile cilia components and multiciliated cell differentiation factors are induced. While the affected astrocytes still retain a single cilium, these organelles elongate and become remarkably distorted. The data suggest that chronic activation of the mitochondrial integrated stress response (ISRmt) in astrocytes drives anabolic metabolism and promotes ciliary elongation. Collectively, our evidence indicates that an active signaling axis involving mitochondria and primary cilia exists and that ciliary signaling is part of ISRmt in astrocytes. We propose that metabolic ciliopathy is a novel pathomechanism for mitochondria-related neurodegenerative diseases.
Identifiants
pubmed: 36383135
pii: 213692
doi: 10.1083/jcb.202203019
pmc: PMC9674092
pii:
doi:
Substances chimiques
Forkhead Transcription Factors
0
FOXJ1 protein, mouse
0
Regulatory Factor X Transcription Factors
0
DNA, Mitochondrial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 Ignatenko et al.
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