Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 Apr 2024
18 Apr 2024
Historique:
received:
04
08
2022
accepted:
08
04
2024
medline:
19
4
2024
pubmed:
19
4
2024
entrez:
18
4
2024
Statut:
epublish
Résumé
Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated mitochondria in both muscles and neurons. We find that endogenous GFP-tagged Cdk8 can be found in both the cytoplasm and nucleus. We show that Cdk8 promotes the phosphorylation of Drp1 at S616, a protein required for mitochondrial fission. Interestingly, Pink1, a mitochondrial kinase implicated in Parkinson's disease, also phosphorylates Drp1 at the same residue. Indeed, overexpression of Cdk8 significantly suppresses the phenotypes observed in flies with low levels of Pink1, including elevated levels of ROS, mitochondrial dysmorphology, and behavioral defects. In summary, we propose that Pink1 and Cdk8 perform similar functions to promote Drp1-mediated fission.
Identifiants
pubmed: 38637532
doi: 10.1038/s41467-024-47623-8
pii: 10.1038/s41467-024-47623-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3326Subventions
Organisme : Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
ID : RGPIN/2014-05479
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT-189990
Organisme : Parkinson Canada
ID : Graduate Fellowship
Informations de copyright
© 2024. The Author(s).
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