Sharapova, Gulnaz; Sabirova, Sirina; Gomzikova, Marina; Brichkina, Anna; Barlev, Nick A; Kalacheva, Natalia V; Rizvanov, Albert; Markov, Nikita; Simon, Hans-Uwe (2024). Mitochondrial Protein Density, Biomass, and Bioenergetics as Predictors for the Efficacy of Glioma Treatments. International journal of molecular sciences, 25(13) MDPI 10.3390/ijms25137038
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Markov, Nikita |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1422-0067 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
16 Jul 2024 14:05 |
Last Modified: |
16 Jul 2024 14:15 |
Publisher DOI: |
10.3390/ijms25137038 |
PubMed ID: |
39000148 |
Uncontrolled Keywords: |
OXPHOS bioenergetics cancer treatment drug response glioblastoma glioma metabolic reprogramming metabolism mitochondria mitochondria-targeting |
BORIS DOI: |
10.48350/198985 |
URI: |
https://boris.unibe.ch/id/eprint/198985 |
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