11. 03. 2026
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At the end of last year, the journal Molecular Medicine (IF 6.4) (open in a new window) published a first-author paper by PhD student Natálie Danešová, focusing on changes in mitochondrial DNA (mtDNA) during colorectal cancer development. The findings suggest that some of these processes may already begin in precancerous stages. The study was carried out in collaboration with colleagues from the Department of Molecular Biology of Cancer and partner institutions.
Until recently, mitochondria were primarily regarded as the “power plants” of the cell. Today, however, it is clear that their role is much broader – and in the case of cancer, also crucial. The study therefore examined how changes in mtDNA are associated with the development of colorectal cancer and whether they might, in the future, help detect the disease at an early stage.
Mitochondria have their own DNA
Mitochondria differ from most other cellular structures in that they contain their own genetic material. This DNA includes genes essential for energy production. The number of mitochondria and the amount of mtDNA vary among cell types and may change during pathological processes.
Damage and instability of mitochondrial DNA
In cancer, including colorectal cancer, mtDNA frequently shows copy-number changes, damage, and alterations in repair mechanisms. Interestingly, studies of colorectal tumours have reported differing results – tumour cells sometimes contain more mtDNA, and sometimes less. An increased copy number is often interpreted as a compensatory response to mitochondrial damage, whereby the cell attempts to maintain energy production despite impaired mitochondrial function.
While the cell nucleus has several sophisticated DNA repair mechanisms at its disposal, mitochondria are considerably more limited in this respect. They can repair mainly small oxidative lesions that arise naturally from reactive oxygen species, a by-product of mitochondrial energy production. However, they are less able to deal with certain other types of damage, which may lead to mtDNA damage accumulating gradually.
What did the research reveal?
The research team focused on three key parameters: the amount of mtDNA, the degree of its damage, and the transcription level of genes involved in DNA or mtDNA repair, measured as mRNA expression. Tissue samples from healthy individuals, patients with benign polyps (adenomas), and patients with colorectal tumours were analysed as part of both a pilot study and a subsequent validation study.
The results showed that both tumour and adenoma tissues exhibited increased mRNA expression of repair genes, whereas the surrounding tissue did not. For some of these genes, a correlation was also observed between mRNA expression levels and the degree of mtDNA damage. This relationship was subsequently confirmed in a larger group of patients.
Another finding was that tissue in the immediate vicinity of the tumour showed a higher level of mtDNA damage than the tumour tissue itself. By contrast, in healthy individuals and in patients with adenomas, the level of mtDNA damage did not differ significantly across tissue types.
Overall, the results suggest that an increase in mtDNA content already occurs at the adenoma stage. In malignant tumours, the mtDNA levels no longer differ markedly, but the tumour cells show increased mRNA expression of the repair genes, which may be associated with the lower level of mtDNA damage observed directly in tumour tissue.
Why is it important?
The research shows that changes in mtDNA and in the mechanisms responsible for its repair appear very early – already in precancerous stages – and occur not only within the tumour itself but also in its immediate surroundings. The finding that neighbouring tissue may exhibit higher levels of mtDNA damage than the tumour suggests that cancer affects a broader tissue environment than previously assumed.
At the same time, the results indicate that tumour cells may have mtDNA repair mechanisms “switched on” at the mRNA level, which could explain why their mitochondria sometimes show lower levels of genetic damage. A better understanding of these processes may, in the future, help refine early diagnosis, distinguish high-risk tissues from healthy ones, and improve our understanding of how healthy tissue gradually transforms into tumour tissue.