biostudies-literatureLiao JZGouvernement du Canada | Natural Sciences and Engineering Research Council of CanadaNICHD NIH HHSParkinson CanadaNINDS NIH HHSNIH HHSGouvernement du Canada | Canadian Institutes of Health Research3326https://www.ebi.ac.uk/biostudies/studies/S-EPMC11026413biostudies-literatureUnknown15(1)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 Nature communicationsCdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.PMC11026413PJT-189990Graduate FellowshipR24 OD031447U54 HD083092P40 OD010949R24 OD022005U54 NS093793RGPIN/2014-05479P40 OD018537Chung HLMarcogliese PCZuo ZKanca OBurns CGSew KDutta DVerheyen EMLiao JZWong KKLNil ZPark YJShih CBellen HJfalseCdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.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 2024-01-01T00:00:00Z2024 Apr2026-05-29T11:26:28.583Z2026-04-08T04:29:04.867ZS-EPMC110264133863753210.1038/s41467-024-47623-8