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Published on: March 28, 2021
Mitochondrial response of glioma cells to temozolomide
Luana Suéling Lenz1, Daphne Torgo1, Julieti Huch Buss1
1Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Biofísica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
Abstract:
Metabolic adaptations are central for carcinogenesis and response to therapy, but little is known about the contribution of mitochondrial dynamics to the response of glioma cells to the standard treatment with temozolomide (TMZ). Glioma cells responded to TMZ with mitochondrial mass increased and the production of round structures of dysfunctional mitochondria. At single-cell level, asymmetric mitosis contributed to the heterogeneity of mitochondrial levels. It affected the fitness of cells in control and treated condition, indicating that the mitochondrial levels are relevant for glioma cell fitness in the presence of TMZ.
Insights
Glioma cells adapt to temozolomide (TMZ) therapy by altering mitochondrial dynamics, increasing mass, and forming dysfunctional mitochondria. Mitochondrial levels impact glioma cell fitness during treatment.
Area of Science:
- Oncology
- Cell Biology
- Mitochondrial Biology
Background:
- Metabolic adaptations are crucial in cancer development and treatment response.
- The role of mitochondrial dynamics in glioma cell response to temozolomide (TMZ) remains largely unexplored.
Purpose of the Study:
- To investigate the contribution of mitochondrial dynamics to glioma cell response to temozolomide (TMZ).
- To understand how mitochondrial levels affect glioma cell fitness under TMZ treatment.
Main Methods:
- Analysis of mitochondrial mass and morphology in glioma cells treated with TMZ.
- Single-cell analysis to assess mitochondrial heterogeneity and its link to cell division.
- Evaluation of cell fitness in relation to mitochondrial levels in control and TMZ-treated conditions.
Main Results:
- Glioma cells exhibited increased mitochondrial mass and developed dysfunctional, rounded mitochondria upon TMZ treatment.
- Asymmetric mitosis was identified as a driver of mitochondrial level heterogeneity at the single-cell level.
- Mitochondrial levels influenced glioma cell fitness in both control and TMZ-treated environments.
Conclusions:
- Mitochondrial dynamics and levels are significantly altered by TMZ treatment in glioma cells.
- Heterogeneity in mitochondrial content, driven by asymmetric mitosis, impacts glioma cell survival during therapy.
- Targeting mitochondrial dynamics may represent a novel therapeutic strategy for gliomas.
