2. Academic Validation
  3. Mitochondrial, metabolic and bioenergetic adaptations drive plasticity of colorectal cancer cells and shape their chemosensitivity

Mitochondrial, metabolic and bioenergetic adaptations drive plasticity of colorectal cancer cells and shape their chemosensitivity

  • Cell Death Dis. 2025 Apr 5;16(1):253. doi: 10.1038/s41419-025-07596-y.
Nikita Markov 1,  Sirina Sabirova 2 3,  Gulnaz Sharapova 2 4,  Marina Gomzikova 2 3,  Anna Brichkina 5,  Nick A Barlev 2 6 7,  Marcel Egger 8,  Albert Rizvanov 4 9,  Hans-Uwe Simon 10 11 12
Affiliations

Affiliations

  • 1 Institute of Pharmacology, University of Bern, Bern, Switzerland.
  • 2 Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
  • 3 Laboratory of Intercellular Communication, Kazan Federal University, Kazan, Russia.
  • 4 OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
  • 5 Institute of Systems Immunology, Center for Tumor Biology and Immunology, Philipps University of Marburg, Marburg, Germany.
  • 6 Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, Russia.
  • 7 Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan.
  • 8 Department of Physiology, University of Bern, Bern, Switzerland.
  • 9 Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, Kazan, Russia.
  • 10 Institute of Pharmacology, University of Bern, Bern, Switzerland. hans-uwe.simon@unibe.ch.
  • 11 Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia. hans-uwe.simon@unibe.ch.
  • 12 Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany. hans-uwe.simon@unibe.ch.
PMID: 40185729 DOI: 10.1038/s41419-025-07596-y
Abstract

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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