한빛사논문
- 조회442
Jenny Zhe Liao 1,2,9, Hyung-lok Chung 3,4,9, Claire Shih 1,2, Kenneth Kin Lam Wong 1,8, Debdeep Dutta 4, Zelha Nil 4, Catherine Grace Burns 4, Oguz Kanca 4, Ye-Jin Park 4, Zhongyuan Zuo 4, Paul C. Marcogliese 5,6, Katherine Sew 1,2, Hugo J. Bellen 4,7,* & Esther M. Verheyen 1,2,*
1Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby V5A1S6 BC, Canada.
2Center for Cell Biology, Development and Disease, Simon Fraser University, Burnaby V5A1S6 BC, Canada.
3Department of Neurology, Houston Methodist Research Institute, Houston, TX, USA.
4Department of Molecular and Human Genetics, Jan and Dan Duncan Neurological Institute, Baylor College of Medicine, Houston, TX 77030, USA.
5Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg R3E0J9 MB, Canada.
6Children’s Hospital Research Institute of Manitoba, Winnipeg R3E3P4 MB, Canada.
7Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
8Present address: Department of Biology, Stanford University, Stanford, CA 94305, USA.
9These authors contributed equally: Jenny Zhe Liao, Hyung-lok Chung.
*Corresponding authors: correspondence to Hugo J. Bellen or Esther M. Verheyen
Abstract
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.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-19)
- 국외 연구진
- 생명과학 > 유전학
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