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Reprogrammed mitochondria help cancer cells with lack of oxygen
As tiny cells' energy power plants, the so-called mitochondria are usually dependent on oxygen, which they "burn" and thus provide energy for the body. If there is no oxygen, the mitochondria can adapt. For example, tumors of the pancreas take advantage of this to grow. However, this is also a potential target for the treatment of pancreatic cancer, according to the latest study by the Max Planck Institute for Biology of Aging.
"Mitochondria burn oxygen and thereby provide energy for the body," the researchers explain in a press release from the Max Planck Society on the study results. If there is a lack of oxygen and nutrients, however, the cells have to change their energy supply quickly. According to the current study, this is done by reprogramming the mitochondria. "Tumors of the pancreas also use this reprogramming, and can continue to spread despite the lack of nutrients and lack of oxygen," the researchers report. The underlying signaling pathway therefore offers a good target for therapies against pancreatic cancer.
Mitochondria switch to glycolysis
Earlier studies have already shown that cells adapt to a lack of oxygen "by switching their energy supply to glycolysis, in which sugar is fermented without oxygen," explains the research team. In the human body, for example, this is often necessary in old age because the cells are poorly supplied with oxygen and nutrients. "It has long been known that cells reduce the number of mitochondria when they switch to glycolysis when there is a lack of oxygen and no longer need them for energy production," says Max Planck Director Professor Dr. Thomas Langer.
Responsible signal path discovered
The researchers have now found that the remaining mitochondria are additionally reprogrammed to meet the new requirements in the event of a lack of oxygen and nutrients. This happens via a newly discovered signal path in the cell. For example, a protease (YME1L) in the membrane of mitochondria is activated when switching to glycolysis and this then breaks down a wide variety of proteins in the organelles.
Signal path with built-in timer
The effect of this protease activation is that no new mitochondria can be formed and the remaining mitochondria change their metabolism. However, the process stops at some point by itself, as the protease begins to degrade itself when the activity is high, the researchers report. "This signal path not only has a built-in timer, but also enables a very quick response to a lack of oxygen," said Prof. Langer.
"Our results identify the mTORC1-LIPIN1-YME1L axis as a regulator of mitochondrial proteostasis at the interface between metabolism and mitochondrial dynamics," the researchers report in the specialist journal "Nature".
Tumor growth significantly reduced
Since the reprogramming of the mitochondria also ensures the growth of the tumors in tumors that are poorly supplied with blood and in which little oxygen and nutrients reach the cancer cells, a blockage of the discovered signal pathway against the cancer cells could be used. This applies, for example, to pancreatic cancer. The researchers therefore used pancreatic cancer cells in the Petri dish to investigate how tumor growth behaves when they switch off the signaling pathway. This significantly reduced tumor growth, the research team reports.
Basis for new treatment approaches
The effect was also confirmed for tumors in the pancreas of mice, according to the Max Planck Society. "There is currently no treatment for pancreatic cancer. I believe that this protease can be a very interesting therapeutic target since we have seen that the signaling pathway is also active in patients with pancreatic cancer, ”emphasizes Professor Langer. So far, however, no substances are known to act on this protease. (fp)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Dipl. Geogr. Fabian Peters
- Max Planck Society: Oxygen deficiency re-programs mitochondria (published November 6, 2019), mpg.de
- Thomas MacVicar, Yohsuke Ohba, Hendrik Nolte, Fiona Carola Mayer, Takashi Tatsuta, Hans-Georg Sprenger, Barbara Lindner, Yue Zhao, Jiahui Li, Christiane Bruns, Marcus Krüger, Markus Habich, Jan Riemer, Robin Schwarzer, Manolis Pasparakis, Sinika Henschke , Jens C. Brüning, Nicola Zamboni, Thomas Langer: Lipid signaling drives proteolytic rewiring of mitochondria by YME1L; in: Nature (published November 6th, 2019), nature.com