ArticleFree radical biology & medicine2015
CDK4-mediated MnSOD activation and mitochondrial homeostasis in radioadaptive protection.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
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- Inhibition of Mitochondrial Antioxidant Defense and CDK4/6 in Mesothelioma.Molecules (Basel, Switzerland) · 2023Article
- Mitochondrial creatine kinase 1 regulates the cell cycle in non-small cell lung cancer via activation of cyclin-dependent kinase 4.Respiratory research · 2023Article
- Induction and assessment of persistent radioresistance in murine leukocytesBiochemistry and biophysics reports · 2022Article
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- COVID-19 and low-dose radiation therapy.Radiation medicine and protection · 2021Review
- MEHP induces alteration of mitochondrial function and inhibition of steroid biosynthesis in MA-10 mouse tumor Leydig cells.Toxicology · 2021Article
- Characterization of Heat Shock Protein 60 as an Interacting Partner of Superoxide Dismutase 2 in the Silkworm,Antioxidants (Basel, Switzerland) · 2021Article
- Review
- Mitochondrial Superoxide Dismutase: What the Established, the Intriguing, and the Novel Reveal About a Key Cellular Redox Switch.Antioxidants & redox signaling · 2020Review
- Cyclin-Dependent Kinase and Antioxidant Gene Expression in Cancers with Poor Therapeutic Response.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Signaling Toward Reactive Oxygen Species-Scavenging Enzymes in Plants.Frontiers in plant science · 2020Review
- Ursolic Acid Regulates Cell Cycle and Proliferation in Colon Adenocarcinoma by Suppressing Cyclin B1.Frontiers in pharmacology · 2020Article
- Manganese Superoxide Dismutase Dysfunction and the Pathogenesis of Kidney Disease.Frontiers in physiology · 2020Review
- Redox regulation of hormone sensitive lipase: Potential role in the mechanism of MEHP-induced stimulation of basal steroid synthesis in MA-10 Leydig cells.Reproductive toxicology (Elmsford, N.Y.) · 2019Article
- Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance.Cancer letters · 2019Review
- Protective effect of polydatin on radiation-induced injury of intestinal epithelial and endothelial cells.Bioscience reports · 2018Article
- Insights into the Dichotomous Regulation of SOD2 in Cancer.Antioxidants (Basel, Switzerland) · 2017Review
- TP53 Mutational Status and ROS Effect the Expression of the Survivin-Associated Radio-Adaptive Response.Radiation research · 2017Article
- Manganese superoxide dismutase and glutathione peroxidase-1 contribute to the rise and fall of mitochondrial reactive oxygen species which drive oncogenesis.Biochimica et biophysica acta. Bioenergetics · 2017Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Mammalian cells are able to sense environmental oxidative and genotoxic conditions such as the environmental low-dose ionizing radiation (LDIR) present naturally on the earth's surface. The stressed cells then can induce a so-called radioadaptive response with an enhanced cellular homeostasis and repair capacity against subsequent similar genotoxic conditions such as a high dose radiation. Manganese superoxide dismutase (MnSOD), a primary mitochondrial antioxidant in mammals, has long been known to play a crucial role in radioadaptive protection by detoxifying O2(•-) generated by mitochondrial oxidative phosphorylation. In contrast to the well-studied mechanisms of SOD2 gene regulation, the mechanisms underlying posttranslational regulation of MnSOD for radioprotection remain to be defined. Herein, we demonstrate that cyclin D1/cyclin-dependent kinase 4 (CDK4) serves as the messenger to deliver the stress signal to mitochondria to boost mitochondrial homeostasis in human skin keratinocytes under LDIR-adaptive radioprotection. Cyclin D1/CDK4 relocates to mitochondria at the same time as MnSOD enzymatic activation peaks without significant changes in total MnSOD protein level. The mitochondrial-localized CDK4 directly phosphorylates MnSOD at serine-106 (S106), causing enhanced MnSOD enzymatic activity and mitochondrial respiration. Expression of mitochondria-targeted dominant negative CDK4 or the MnSOD-S106 mutant reverses LDIR-induced mitochondrial enhancement and adaptive protection. The CDK4-mediated MnSOD activation and mitochondrial metabolism boost are also detected in skin tissues of mice receiving in vivo whole-body LDIR. These results demonstrate a unique CDK4-mediated mitochondrial communication that allows cells to sense environmental genotoxic stress and boost mitochondrial homeostasis by enhancing phosphorylation and activation of MnSOD.
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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.