MitoQ Triggers Mitochondrial Collapse and Apoptotic Death in Glioblastoma Associated with KATP Channel Expression Changes

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dc.contributor.authorKaraaslan, Alp
dc.contributor.authorHacioglu, Ceyhan
dc.date.accessioned2026-07-01T11:40:12Z
dc.date.available2026-07-01T11:40:12Z
dc.date.issued2026
dc.departmentDüzce Üniversitesi
dc.description.abstractGlioblastoma (GBM) is the most aggressive primary brain tumor and remains refractory to current therapies due to its pronounced metabolic heterogeneity and mitochondrial adaptability. Ion channels, particularly ATP-sensitive-potassium (KATP) channels, have emerged as critical regulators of cellular energy sensing in cancer. This study evaluated the mitochondrial-targeted agent MitoQ in GBM and explored its potential association with KATP channels. In this study, the cytotoxic potential of MitoQ was systematically evaluated in three genetically distinct GBM cell lines. Cell viability was assessed using concentration-response analyses to identify differential sensitivity. Baseline expression of KATP-channel components (KCNJ11/Kir6.2, ABCC8/SUR1, and CCDC51) was quantified by qRT-PCR and Western blotting. Mechanistic analyses were subsequently performed in the most sensitive cell line and included mitochondrial ROS measurement (MitoSOX), confocal assessment of mitochondrial morphology, Seahorse XF-based bioenergetic profiling, ATP/ADP ratio quantification, analysis of autophagic flux via LC3-II/p62 turnover with bafilomycin-A1, and caspase-3/7-based apoptosis detection. U87 cells exhibited the lowest IC50 for MitoQ and showed significantly higher baseline expression of KATP channel subunits compared to U251 and T98G cells. Acute MitoQ exposure (10 & micro;M, 6 h) in U87 cells induced marked mitochondrial superoxide accumulation, extensive mitochondrial fragmentation, severe suppression of oxidative phosphorylation, and ATP depletion. These effects were associated with selective downregulation of Kir6.2 and the mitochondrial KATP-associated component CCDC51, impaired autophagic flux with p62 accumulation, and robust activation of executioner caspases. In conclusion, MitoQ may induce mitochondrial dysfunction in metabolically primed GBM cells, and cellular sensitivity appears to correlate with a distinct KATP channel expression signature.
dc.identifier.doi10.1007/s11064-026-04742-6
dc.identifier.issn0364-3190
dc.identifier.issn1573-6903
dc.identifier.issue2
dc.identifier.pmid41910839
dc.identifier.scopus2-s2.0-105034704223
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1007/s11064-026-04742-6
dc.identifier.urihttps://hdl.handle.net/20.500.12684/23669
dc.identifier.volume51
dc.identifier.wosWOS:001728983300002
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer/Plenum Publishers
dc.relation.ispartofNeurochemical Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260623
dc.subject[Keyword Not Available]
dc.titleMitoQ Triggers Mitochondrial Collapse and Apoptotic Death in Glioblastoma Associated with KATP Channel Expression Changes
dc.typeArticle

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