ArticleJournal of experimental & clinical cancer research : CR2024
Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Mitophagy coordinates organelle crosstalk in health and diseases.Signal transduction and targeted therapy · 2026Review
- Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy.CNS neuroscience & therapeutics · 2026Review
- Article
- Metabolic remodeling of endometriosis microenvironment: Energy stress and immune evasion.iScience · 2026Review
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction.Translational neurodegeneration · 2026Article
- ITPR1 Maintains Mitochondrial Redox Homeostasis to Drive Glioblastoma Progression Through Recruitment and Activation of DRP1.Antioxidants (Basel, Switzerland) · 2026Article
- SIRT5-RNF126 coordinated regulation of METTL17 stability controls mitochondrial function and glioma progression.Cell & bioscience · 2026Article
- Development and validation of a prognosis model for low-grade gliomas based on metabolic gene risk scoring and immune microenvironment interaction.Discover oncology · 2026Article
- Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- The role of FIS1 and its post-translational modifications in diseases and health damage caused by environmental pollution.Cell biology and toxicology · 2025Review
- Research on the interactive mechanisms between mitochondrial variations and immune responses in gliomas based on integrated visualization analysis.Discover oncology · 2025Review
- Mitochondrial dysfunction in adipocyte differentiation: implications for obesity and metabolic syndrome intervention.Acta biochimica et biophysica Sinica · 2025Article
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
- Crosstalk between mitochondrial dysfunction and benign prostatic hyperplasia: unraveling the intrinsic mechanisms.The Canadian journal of urology · 2025Review
- Fis1 regulates mitochondrial morphology, bioenergetics and removal of mitochondrial DNA damage in irradiated glioblastoma cells.Journal of cell science · 2025Article
- Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.Contemporary oncology (Poznan, Poland) · 2025Review
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Authors and funding
16 authors.
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Abstract
backgroundThe dynamics of mitochondrial respiratory cristae (MRC) and its impact on oxidative phosphorylation (OXPHOS) play a crucial role in driving the progression of high-grade glioma (HGG). However, the underlying mechanism remains unclear.
methodsIn the present study, we employed machine learning-based transmission electron microscopy analysis of 7141 mitochondria from 54 resected glioma patients. Additionally, we conducted bioinformatics analysis and multiplex immunohistochemical (mIHC) staining of clinical glioma microarrays to identify key molecules involved in glioma. Subsequently, we modulated the expression levels of mitochondrial dynamic-1-like protein (DNM1L/DRP1), and its two receptors, mitochondrial fission protein 1 (FIS1) and mitochondrial fission factor (MFF), via lentiviral transfection to further investigate the central role of these molecules in the dynamics of glioblastoma (GBM) cells and glioma stem cells (GSCs). We then evaluated the potential impact of DNM1L/DRP1, FIS1, and MFF on the proliferation and progression of GBM cells and GSCs using a combination of CCK-8 assay, Transwell assay, Wound Healing assay, tumor spheroid formation assay and cell derived xenograft assay employing NOD/ShiLtJGpt-Prkdc
resultsOur findings revealed that compared to low-grade glioma (LGG), HGG exhibited more integrated MRC structures. Further research revealed that DNM1L/DRP1, FIS1, and MFF played pivotal roles in governing mitochondrial fission and remodeling MRC in HGG. The subsequent validation demonstrated that DNM1L/DRP1 exerts a positive regulatory effect on FIS1, whereas the interaction between MFF and FIS1 demonstrates a competitive inhibition relationship. The down-regulation of the DNM1L/DRP1-FIS1 axis significantly impaired mitophagy, thereby hindering the remodeling of MRC and inhibiting OXPHOS function in glioma, ultimately leading to the inhibition of its aggressive progression. In contrast, MFF exerts a contrasting effect on MRC integrity, OXPHOS activity, and glioma progression.
conclusionsThis study highlights that the DNM1L/DRP1-FIS1 axis stabilizes MRC structures through mitophagy in HGG cells while driving their OXPHOS activity ultimately leading to robust disease progression. The inhibition of the DNM1L/DRP1-FIS1 axis hinders MRC remodeling and suppresses GBM progression. We propose that down-regulation of the DNM1L/DRP1-FIS1 axis could be a potential therapeutic strategy for treating HGG.
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