Mitochondrial, metabolic and bioenergetic adaptations drive plasticity of colorectal cancer cells and shape their chemosensitivity
Markov N. Sabirova S. Sharapova G. Gomzikova M. Brichkina A. Barlev N.A. Egger M. Rizvanov A. Simon H.-U.
December 2025Springer Nature
Cell Death and Disease
2025#16Issue 1
The extent of mitochondrial heterogeneity and the presence of mitochondrial archetypes in cancer remain unknown. Mitochondria play a central role in the metabolic reprogramming that occurs in cancer cells. This process adjusts the activity of metabolic pathways to support growth, proliferation, and survival of cancer cells. Using a panel of colorectal cancer (CRC) cell lines, we revealed extensive differences in their mitochondrial composition, suggesting functional specialisation of these organelles. We differentiated bioenergetic and mitochondrial phenotypes, which point to different strategies used by CRC cells to maintain their sustainability. Moreover, the efficacy of various treatments targeting metabolic pathways was dependent on the respiration and glycolysis levels of cancer cells. Furthermore, we identified metabolites associated with both bioenergetic profiles and cell responses to treatments. The levels of these molecules can be used to predict the therapeutic efficacy of anti-cancer drugs and identify metabolic vulnerabilities of CRC. Our study indicates that the efficacy of CRC therapies is closely linked to mitochondrial status and cellular bioenergetics.
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Institute of Pharmacology, University of Bern, Bern, Switzerland
Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation
Laboratory of Intercellular Communication, Kazan Federal University, Kazan, Russian Federation
OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation
Institute of Systems Immunology, Center for Tumor Biology and Immunology, Philipps University of Marburg, Marburg, Germany
Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, Russian Federation
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan
Department of Physiology, University of Bern, Bern, Switzerland
Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, Kazan, Russian Federation
Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
Institute of Pharmacology
Laboratory of Molecular Immunology
Laboratory of Intercellular Communication
OpenLab Gene and Cell Technology
Institute of Systems Immunology
Institute of Cytology of the Russian Academy of Sciences
Department of Biomedical Sciences
Department of Physiology
Division of Medical and Biological Sciences
Institute of Biochemistry
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