ArticleNeuro-oncology2015
Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma.
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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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28citing papers in PubMed, 1 pooled it
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- A systematic review on the biochemical threshold of mitochondrial genetic variants.Genome research · 2024Pooled it
- "NanoDel": identification of large-scale mitochondrial DNA deletions using long-read sequencing.Bioinformatics (Oxford, England) · 2026Article
- Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy.CNS neuroscience & therapeutics · 2026Review
- Mitochondria transfer in glioblastoma.Neuro-oncology · 2026Review
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- Mitochondrial electron transport chain gene-based prognostic model identifies SDHB as a key regulator of low-grade glioma progression and therapeutic target.Cancer cell international · 2025Article
- Glioma grade and mortality in relation to sequence variation in the mitochondrial genome.Cancer genetics · 2025Article
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.Contemporary oncology (Poznan, Poland) · 2025Review
- Mitochondrial quality control and transfer communication in neurological disorders and neuroinflammation.Frontiers in immunology · 2025Review
- Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model.International journal of molecular sciences · 2024Review
- Reactive oxygen species induced by indomethacin enhance accumulation of heme carrier protein 1 and hematoporphyrin accumulationJournal of clinical biochemistry and nutrition · 2024Article
- Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Metabolic Rewiring in Adult-Type Diffuse Gliomas.International journal of molecular sciences · 2023Review
- Large Common Mitochondrial DNA Deletions Are Associated with a Mitochondrial SNP T14798C Near the 3' Breakpoints.Complex psychiatry · 2023Article
- Mitochondrial DNA Changes in Genes of Respiratory Complexes III, IV and V Could Be Related to Brain Tumours in Humans.International journal of molecular sciences · 2022Article
- Identification of Mitochondrial DNA Variants Associated With Risk of Neuroblastoma.Journal of the National Cancer Institute · 2022Article
- Mitochondrial DNA sequence variation and risk of glioma.Mitochondrion · 2022Article
- Mitochondrial DNA Alterations in Glioblastoma (GBM).International journal of molecular sciences · 2021Review
- Mitochondrial DNA abnormalities provide mechanistic insight and predict reactive oxygen species-stimulating drug efficacy.BMC cancer · 2021Article
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 2 countries.
Rhiannon E LloydBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Kathleen KeatleyBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
D Timothy J LittlewoodBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Brigitte MeunierBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
William V HoltBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Qian AnBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Samantha C HigginsBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Stavros PolyzoidisBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Katie F StephensonBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Keyoumars AshkanBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Helen L FillmoreBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
Geoffrey J PilkingtonBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
John E McGeehanBrain Tumour Research Centre (R.E.L., K.K., S.C.H., K.F.S., H.L.F., G.J.P.), Molecular Biophysics Laboratories (K.K., J.E.M.), Epigenetics and Developmental Biology Laboratories (Q.A.), Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK; Department of Life Sciences, Natural History Museum, London, UK (D.T.J.L.); Institut de Biologie Intégrative de la Cellule, Paris-Saclay University, CEA, CNRS, Université Paris-Sud, Gif sur Yvette, France (B.M.); Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK (W.V.H.); Department of Neurosurgery, Kings College Hospital, London, UK (S.P., K.A.).
University of Sheffield · GBCentre National de la Recherche Scientifique · FRInstitut de Biologie Intégrative de la Cellule · FRBrain Tumour Research · GBCEA Paris-Saclay · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRKing's College Hospital · GBUniversité Paris-Saclay · FRUniversité Paris-Sud · FR
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma (GBM) is the most common primary brain tumor in adults, with a dismal prognosis. Treatment is hampered by GBM's unique biology, including differential cell response to therapy. Although several mitochondrial abnormalities have been identified, how mitochondrial DNA (mtDNA) mutations contribute to GBM biology and therapeutic response remains poorly described. We sought to determine the spectrum of functional complex III and IV mtDNA mutations in GBM.
methodsThe complete mitochondrial genomes of 10 GBM cell lines were obtained using next-generation sequencing and combined with another set obtained from 32 GBM tissues. Three-dimensional structural mapping and analysis of all the nonsynonymous mutations identified in complex III and IV proteins was then performed to investigate functional importance.
resultsOver 200 mutations were identified in the mtDNAs, including a significant proportion with very low mutational loads. Twenty-five were nonsynonymous mutations in complex III and IV, 9 of which were predicted to be functional and affect mitochondrial respiratory chain activity. Most of the functional candidates were GBM specific and not found in the general population, and 2 were present in the germ-line. Patient-specific maps reveal that 43% of tumors carry at least one functional candidate.
conclusionsWe reveal that the spectrum of GBM-associated mtDNA mutations is wider than previously thought, as well as novel structural-functional links between specific mtDNA mutations, abnormal mitochondria, and the biology of GBM. These results could provide tangible new prognostic indicators as well as targets with which to guide the development of patient-specific mitochondrially mediated chemotherapeutic approaches.
Indexed as
DNA, MitochondrialAdolescentAdultAgedBrain NeoplasmsElectron Transport Complex IIIElectron Transport Complex IVFemaleGlioblastomaHumansMaleMiddle AgedMolecular Docking SimulationMutationDNA, MitochondrialElectron Transport Complex IIIElectron Transport Complex IVfunctional predictionglioblastomamitochondrial DNA (mtDNA) mutationstructural analysissubgrouping
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