ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Regulation of Bcl-xL-ATP Synthase Interaction by Mitochondrial Cyclin B1-Cyclin-Dependent Kinase-1 Determines Neuronal Survival.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
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- Perinatal liver sympathetic innervation governs body size.Communications biology · 2026Article
- Controlling gene expression through five zinc finger domains of ZNF18.Protein science : a publication of the Protein Society · 2025Article
- 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
- Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties.International journal of molecular sciences · 2024Article
- Cross-talk between energy and redox metabolism in astrocyte-neuron functional cooperation.Essays in biochemistry · 2023Review
- Article
- APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer's disease.Frontiers in pharmacology · 2022Review
- Amyloid-β Induces Cdh1-Mediated Rock2 Stabilization Causing Neurodegeneration.Frontiers in pharmacology · 2022Article
- ATP Synthase and Mitochondrial Bioenergetics Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Preconditioning-Activated AKT Controls Neuronal Tolerance to Ischemia through the MDM2-p53 Pathway.International journal of molecular sciences · 2021Article
- Article
- Involvement of Bcl-xL in Neuronal Function and Development.International journal of molecular sciences · 2021Review
- Oxidative stress battles neuronal Bcl-xL in a fight to the death.Neural regeneration research · 2021Article
- Cell Death Related Proteins Beyond Apoptosis in the CNS.Frontiers in cell and developmental biology · 2021Review
- Refocusing the Brain: New Approaches in Neuroprotection Against Ischemic Injury.Neurochemical research · 2021Review
- Core cell cycle machinery is crucially involved in both life and death of post-mitotic neurons.Cellular and molecular life sciences : CMLS · 2020Review
- Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke.Science advances · 2020Article
- Review
- ATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration.Journal of molecular and cellular cardiology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The survival of postmitotic neurons needs continuous degradation of cyclin B1, a mitotic protein accumulated aberrantly in the damaged brain areas of Alzheimer's disease and stroked patients. Degradation of cyclin B1 takes place in the proteasome after ubiquitylation by the anaphase-promoting complex/cyclosome (APC/C)-cadherin 1 (Cdh1), an E3 ubiquitin ligase that is highly active in neurons. However, during excitotoxic damage-a hallmark of neurological disorders-APC/C-Cdh1 is inactivated, causing cyclin B1 stabilization and neuronal death through an unknown mechanism. Here, we show that an excitotoxic stimulus in rat cortical neurons in primary culture promotes cyclin B1 accumulation in the mitochondria, in which it binds to, and activates, cyclin-dependent kinase-1 (Cdk1). The cyclin B1-Cdk1 complex in the mitochondria phosphorylates the anti-apoptotic protein B-cell lymphoma extra-large (Bcl-xL), leading to its dissociation from the β subunit of F1Fo-ATP synthase. The subsequent inhibition of ATP synthase activity causes complex I oxidative damage, mitochondrial inner membrane depolarization, and apoptotic neuronal death. These results unveil a previously unrecognized role for mitochondrial cyclin B1 in the oxidative damage associated with neurological disorders.
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Registered trials
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.