ArticleProteome science2020
NEK10 interactome and depletion reveal new roles in mitochondria.
Article in Proteome science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Klotho-Derived Peptide 1 Protects against Acute Kidney Injury by Directly Targeting Mitochondrial ATAD3A.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PFDN2 stabilizes PYCR2 to activate Wnt/β-catenin signaling and promote colorectal cancer progression.Scientific reports · 2026Article
- Extracellular matrix-derived mechanical force induces CDK4/6 inhibitor resistance by inhibiting NEK10 dependent cell cycle regulation in breast cancer.International journal of surgery (London, England) · 2026Article
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- NEK kinases in cell cycle regulation, DNA damage response, and cancer progression.Tissue & cell · 2025Review
- Clinical characteristics and induced pluripotent stem cells (iPSCs) disease model of Harel-Yoon syndrome caused by compound heterozygous ATAD3A variants.Human cell · 2025Article
- NEK10 kinase ablation affects mitochondrial morphology, function and protein phosphorylation status.Proteome science · 2024Article
- NEKL-4 regulates microtubule stability and mitochondrial health in ciliated neurons.The Journal of cell biology · 2024Article
- The Mitochondrial Connection: The Nek Kinases' New Functional Axis in Mitochondrial Homeostasis.Cells · 2024Review
- NEKL-4 regulates microtubule stability and mitochondrial health inbioRxiv : the preprint server for biology · 2024Article
- ATAD3A: A Key Regulator of Mitochondria-Associated Diseases.International journal of molecular sciences · 2023Review
- NEK Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types.Cancers · 2023Review
- Article
- mtDNA Maintenance and Alterations in the Pathogenesis of Neurodegenerative Diseases.Current neuropharmacology · 2023Review
- Cuproptosis-a potential target for the treatment of osteoporosis.Frontiers in endocrinology · 2023Review
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Integrative Analysis of the Expression Levels and Prognostic Values for NEK Family Members in Breast Cancer.Frontiers in genetics · 2022Article
- Cuproptosis and cuproptosis-related genes in rheumatoid arthritis: Implication, prospects, and perspectives.Frontiers in immunology · 2022Review
- Identification of a novel histone phosphorylation prognostic signature in hepatocellular carcinoma based on bulk and single-cell RNA sequencing.Frontiers in endocrinology · 2022Article
- CTLA-4 Facilitates DNA Damage-Induced Apoptosis by Interacting With PP2A.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMembers of the family of NEK protein kinases (NIMA-related kinases) were described to have crucial roles in regulating different aspects of the cell cycle. NEK10 was reported to take part in the maintenance of the G2/M checkpoint after exposure to ultraviolet light. NEK1, NEK5, NEK2 and NEK4 proteins on the other hand have been linked to mitochondrial functions.
methodsHEK293T cells were transfected with FLAG empty vector or FLAG-NEK10 and treated or not with Zeocin. For proteomic analysis, proteins co-precipitated with the FLAG constructs were digested by trypsin, and then analyzed via LC-MS/MS. Proteomic data retrieved were next submitted to Integrated Interactome System analysis and differentially expressed proteins were attributed to Gene Ontology biological processes and assembled in protein networks by Cytoscape. For functional, cellular and molecular analyses two stable Nek10 silenced HeLa cell clones were established.
resultsHere, we discovered the following possible new NEK10 protein interactors, related to mitochondrial functions: SIRT3, ATAD3A, ATAD3B, and OAT. After zeocin treatment, the spectrum of mitochondrial interactors increased by the proteins: FKBP4, TXN, PFDN2, ATAD3B, MRPL12, ATP5J, DUT, YWHAE, CS, SIRT3, HSPA9, PDHB, GLUD1, DDX3X, and APEX1. We confirmed the interaction of NEK10 and GLUD1 by proximity ligation assay and confocal microscopy. Furthermore, we demonstrated that NEK10-depleted cells showed more fragmented mitochondria compared to the control cells. The knock down of NEK10 resulted further in changes in mitochondrial reactive oxygen species (ROS) levels, decreased citrate synthase activity, and culminated in inhibition of mitochondrial respiration, affecting particularly ATP-linked oxygen consumption rate and spare capacity. NEK10 depletion also decreased the ratio of mtDNA amplification, possibly due to DNA damage. However, the total mtDNA content increased, suggesting that NEK10 may be involved in the control of mtDNA content.
conclusionsTaken together these data place NEK10 as a novel regulatory player in mitochondrial homeostasis and energy metabolism.
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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.