ArticleHuman molecular genetics2015
CDK5 phosphorylates DRP1 and drives mitochondrial defects in NMDA-induced neuronal death.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 85 citations in OpenAlex.
- Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- DRP1, fission and apoptosis.Cell death discovery · 2025Review
- DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.Nature communications · 2024Article
- Roscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro.International journal of molecular sciences · 2024Article
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Manipulating mitochondrial reactive oxygen species alters survival in unexpected ways in a Drosophila Cdk5 model of neurodegeneration.Biology open · 2024Article
- Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of CaScientific reports · 2024Article
- Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior.iScience · 2024Article
- DLK-dependent axonal mitochondrial fission drives degeneration following axotomy.bioRxiv : the preprint server for biology · 2024Article
- Molecular mechanisms underlying TNFα-induced mitochondrial fragmentation in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Mitigating aberrant Cdk5 activation alleviates mitochondrial defects and motor neuron disease symptoms in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.Cell cycle (Georgetown, Tex.) · 2023Article
- Mitophagy for cardioprotection.Basic research in cardiology · 2023Review
- Mechanisms of Modulation of Mitochondrial Architecture.Biomolecules · 2023Review
- CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer's disease.Cell death and differentiation · 2022Article
- Decoupling dedifferentiation and G2/M arrest in kidney fibrosis.The Journal of clinical investigation · 2022Article
- Cardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy.Nature communications · 2022Article
- Mitochondrial HSF1 triggers mitochondrial dysfunction and neurodegeneration in Huntington's disease.EMBO molecular medicine · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Defects in mitochondrial fission and cyclin dependent kinase 5 (CDK5) activation are early events that precede neuronal loss following NMDA-induced neuronal death. Here, we report that the cytoplasmic CDK5 tightly regulates mitochondrial morphology defects associated with NMDA-induced neuronal injury via regulation of the mitochondrial fission protein, dynamin-related protein 1 (DRP1). We show that DRP1 is a direct target of CDK5. CDK5-mediated phosphorylation of DRP1 at a conserved Serine residue, S585, is elevated at the mitochondria and is associated with increased mitochondrial fission. Ectopic expression of a cytoplasmic CDK5 or mutant DRP1-S585D results in increased mitochondrial fragmentation in primary neurons. Conversely, expression of a dominant negative form of cytoplasmic CDK5 or mutant DRP1-S585A results in elongated mitochondria. In addition, pharmacological inhibition of CDK5 by Roscovitine inhibits DRP1 phosphorylation and mitochondrial fission associated with NMDA-induced neuronal loss. Importantly, conditional deletion of CDK5 significantly attenuates DRP1 phosphorylation at S585 and rescues mitochondrial fission defects in neurons exposed to NMDA. Our studies delineate an important mechanism by which CDK5 regulates mitochondrial morphology defects associated with neuronal injury.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.