Evidence map›Paper›PMID 41140169›Full record

ArticleRadiology and oncology2025

Heterogenous mitochondrial ultrastructure and metabolism of human glioblastoma cells: differences between stem-like and differentiated cancer cells in response to chemotherapy.

Urban Bogataj, Metka Novak, Simona Katrin Galun, Klementina Fon Tacer, Milos Vittori, Cornelis J F Van Noorden, Barbara Breznik

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Article in Radiology and oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Urban Bogataj1University of Ljubljana, Biotechnical Faculty, Department of Biology, Ljubljana, Slovenia.
Metka Novak2National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Ljubljana, Slovenia.
Simona Katrin Galun2National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Ljubljana, Slovenia.
Klementina Fon Tacer5Texas Tech University School of Veterinary Medicine, Amarillo, Texas, USA.
Milos Vittori1University of Ljubljana, Biotechnical Faculty, Department of Biology, Ljubljana, Slovenia.
Cornelis J F Van Noorden2National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Ljubljana, Slovenia.
Barbara Breznik2National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Ljubljana, Slovenia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlioblastoma stem-like cells (GSCs) contribute to the resistance of glioblastoma (GBM) tumors to standard therapies. The background of the resistance of GSCs to the chemotherapeutic agent temozolomide is not yet fully understood in the context of cellular metabolism and the role of mitochondria. The aim of this study was to perform a detailed ultrastructural characterization of the mitochondria of GSCs prior and post temozolomide exposure and to compare it to differentiated GBM cells. MATERIALS AND

methodsPatient-derived and established GBM cell lines were used for the study. The ultrastructure of the mitochondria of the examined cell lines was assessed by transmission electron microscopy. The microscopic analysis was complemented and compared by an analysis of cell metabolism using Seahorse extracellular flux analysis.

resultsWe found that the metabolic profile of GSCs is quiescent and aerobic. Their elongated mitochondria with highly organized cristae are indicating increased biogenesis and mitochondrial fusion and corresponds to a more oxidative phosphorylation (OXPHOS)-dependent metabolism. The metabolism of GSCs is dependent on OXPHOS and there are no changes in defective mitochondria fraction after the treatment with temozolomide. In contrast, differentiated GBM cells with fragmented mitochondria, which have less organized cristae, are more energetic and glycolytic. Temozolomide treatment induced ultrastructural mitochondrial damage in differentiated GBM cells.

conclusionsWe demonstrated differences in mitochondrial ultrastructure and cellular metabolism between GSCs and differentiated GBM cells in response to temozolomide, suggesting that mitochondria play an important role in the resistance of GSCs to temozolomide. This study provides a basis for further studies addressing GSC chemotherapy resistance in the context of mitochondrial structure and function.

Indexed as

Antineoplastic Agents, AlkylatingBrain NeoplasmsDacarbazineGlioblastomaMitochondriaNeoplastic Stem CellsCell DifferentiationCell Line, TumorDrug Resistance, NeoplasmHumansMicroscopy, Electron, TransmissionOxidative PhosphorylationTemozolomideAntineoplastic Agents, AlkylatingDacarbazineTemozolomidechemotherapy resistanceglioblastomametabolismmitochondria ultrastructurestem cells

Identifiers

PMID41140169
PMCPMC12707455

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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 Socratic graph.