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When cells are in crisis: How does UPRmt become a key weapon against cancer?
With the advancement of scientific research, more and more evidence shows the importance of the intracellular unfolded protein response (UPRmt) in cells dealing with stress and maintaining the stability of the internal environment. Especially in the context of cancer, researchers have begun to explore in depth how UPRmt becomes an important weapon for cells to fight cancer.
Mechanism and function of UPRmt
UPRmt is a cellular stress response that occurs primarily within mitochondria. When proteins within mitochondria are not properly folded, it is activated and initiates a series of biological responses to restore stability. When cells are stressed, UPRmt promotes the expression of protein-folding chaperones and proteases to help clean up unfolded proteins.
"The activation of UPRmt can enhance the activity of antioxidant enzymes and promote the autophagy process, which is crucial for the proliferation of cancer cells."
Association of UPRmt with lifespan extension
The study found a strong association between UPRmt and increased lifespan. For example, in C. elegans, mutations in the mitochondrial electron transport chain not only extend lifespan but also activate UPRmt. In addition, increasing NAD+ levels by supplementing nicotinamide or nicotinamide riboside can also extend the lifespan of these organisms, further confirming the important regulatory role of UPRmt in biological organisms.
UPRmt cellular responses and cancer association
Researchers have linked UPRmt to the transformation of cancer cells. They explored the role of SIRT3 in UPRmt and found that it became an important indicator for distinguishing metastatic and non-metastatic tumor cells. As cancer cells undergo a shift in their energy acquisition strategy from aerobic phosphorylation to aerobic glycolysis, UPRmt is believed to be critical for maintaining mitochondrial integrity in cancer.
"Studies have shown that inhibiting UPRmt, especially ATF5, can selectively kill cancer cells while having little effect on normal cells."
Association of UPRmt with inflammatory bowel disease
Recent studies have also pointed to a potential role for UPRmt in infectious bowel diseases such as Crohn's disease and ulcerative colitis. These intestinal diseases are associated with mitochondrial dysfunction in the intestinal epithelium, and activation of the UPRmt has been observed in mouse models and in patients with intestinal diseases. In particular, mitochondrial dysfunction and UPRmt activation are associated with intestinal stem cell function and Paneth cell necrosis.
Further research directions
As our understanding of UPRmt deepens, many related studies will help us better fight cancer and may provide new perspectives for treating other related diseases. Through further research, scientists hope to clarify the role of UPRmt in the stability of the internal cell environment and cancer resistance, and apply it to the prevention and treatment of diseases.
In future biomedical research, how should we use the UPRmt mechanism to fight various diseases?
