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Mitochondrial Protein Density, Biomass, and Bioenergetics as Predictors for the Efficacy of Glioma Treatments.
Sharapova, Gulnaz; Sabirova, Sirina; Gomzikova, Marina; Brichkina, Anna; Barlev, Nick A; Kalacheva, Natalia V; Rizvanov, Albert; Markov, Nikita; Simon, Hans-Uwe.
Afiliação
  • Sharapova G; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
  • Sabirova S; OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
  • Gomzikova M; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
  • Brichkina A; Laboratory of Intercellular Communication, Kazan Federal University, 420111 Kazan, Russia.
  • Barlev NA; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
  • Kalacheva NV; Laboratory of Intercellular Communication, Kazan Federal University, 420111 Kazan, Russia.
  • Rizvanov A; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
  • Markov N; Institute of Systems Immunology, Center for Tumor Biology and Immunology, Philipps University of Marburg, 35043 Marburg, Germany.
  • Simon HU; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Int J Mol Sci ; 25(13)2024 Jun 27.
Article em En | MEDLINE | ID: mdl-39000148
ABSTRACT
The metabolism of glioma cells exhibits significant heterogeneity and is partially responsible for treatment outcomes. Given this variability, we hypothesized that the effectiveness of treatments targeting various metabolic pathways depends on the bioenergetic profiles and mitochondrial status of glioma cells. To this end, we analyzed mitochondrial biomass, mitochondrial protein density, oxidative phosphorylation (OXPHOS), and glycolysis in a panel of eight glioma cell lines. Our findings revealed considerable variability mitochondrial biomass varied by up to 3.2-fold, the density of mitochondrial proteins by up to 2.1-fold, and OXPHOS levels by up to 7.3-fold across the cell lines. Subsequently, we stratified glioma cell lines based on their mitochondrial status, OXPHOS, and bioenergetic fitness. Following this stratification, we utilized 16 compounds targeting key bioenergetic, mitochondrial, and related pathways to analyze the associations between induced changes in cell numbers, proliferation, and apoptosis with respect to their steady-state mitochondrial and bioenergetic metrics. Remarkably, a significant fraction of the treatments showed strong correlations with mitochondrial biomass and the density of mitochondrial proteins, suggesting that mitochondrial status may reflect glioma cell sensitivity to specific treatments. Overall, our results indicate that mitochondrial status and bioenergetics are linked to the efficacy of treatments targeting metabolic pathways in glioma.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosforilação Oxidativa / Biomassa / Proteínas Mitocondriais / Metabolismo Energético / Glioma / Mitocôndrias Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Federação Russa

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosforilação Oxidativa / Biomassa / Proteínas Mitocondriais / Metabolismo Energético / Glioma / Mitocôndrias Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Federação Russa