Chemists from Lomonosov Moscow State University (MSU), together with their colleagues, have developed a molecular tool that can boost the activity of mitochondria, cellular structures involved in energy production. In experiments, activating mitochondrial metabolism slowed the proliferation of cancer cells and the growth of melanoma tumors in mice. The findings were published in the journal Nature Chemical Biology.
In the human body, glucose is converted into carbon dioxide through several stages. First, it is broken down into pyruvate, which then enters the mitochondria, where it is oxidized into carbon dioxide with the help of oxygen, Nauka Rossii reports. However, in many tumor cells, even when sufficient oxygen is available, the first stage—glucose breakdown—predominates. Since pyruvate enters the mitochondria inefficiently, its oxidation is also reduced. This phenomenon is known as the Warburg effect. The researchers therefore set out to determine how forcibly boosting mitochondrial activity would affect tumor cells.
To investigate this question, the authors developed a molecular tool called Grubraw, a name derived by reversing the word "Warburg." It enables pyruvate to be produced directly inside mitochondria. This approach helps overcome the limitations that restrict pyruvate entry into mitochondria and enhances oxidative metabolic processes.
In experiments involving cancer cells, activation of Grubraw increased mitochondrial respiration and reduced the rate of cell proliferation in most of the cell models studied.
The researchers also tested the tool in mice bearing tumors formed from human melanoma cells. Activation of Grubraw slowed tumor growth.
The analysis also showed that increased mitochondrial activity was accompanied by changes in the expression of genes involved in the cell cycle, cell division and DNA replication. At the same time, tumor cells partially compensated for the increased mitochondrial metabolism by exporting excess pyruvate produced as a result beyond the cell membrane.
The NMR-based metabolomic analysis for the study was conducted by Sofya Maryasina, a senior researcher at the MSU Faculty of Chemistry.
"Changes in metabolism make it possible to see how interference with mitochondrial activity affects cellular metabolism. In this study, NMR-based metabolomic analysis complemented other research methods and helped characterize the metabolic changes accompanying mitochondrial activation in tumor cells," she said.
The study demonstrates that the metabolic characteristics of tumor cells may not simply be a consequence of their rapid growth, but also one of the factors regulating cell proliferation. The findings expand our understanding of the role of mitochondria in tumor development and may help researchers explore new approaches to targeting tumor metabolism. However, further studies will be needed to assess whether this approach could eventually be used in cancer treatment.
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