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Hungry cells, on a binge, know their own limits

14 July 2010 NWO (Netherlands Organization for Scientific Research)

Cells that consume parts of themselves can stop this process autonomously as well. This was discovered by NWO researcher Judith Klumperman's group, in collaboration with colleagues from the National Institute of Health in Washington. The self-cannibalism is part of the normal digestive process of the cell, but also a survival mechanism in times of famine. This is what makes it difficult for doctors to 'starve out' cancer cells, for instance. The research results were published on 6 June in Nature.

Cells require food, just like people, and excrete products after the food has been digested, Furthermore, just as people can use up their own reserves of fat, cells can use their own products as a fuel. This is called autophagy. How cells reached the stage of being able to digest themselves was already clear, but researchers were in the dark about the consequences of this. Klumperman and her colleagues discovered that a single enzyme ensures the cell does not consume itself entirely, whether in rats, fish, birds or people: the enzyme mTOR.
Halting the binge

Cells must be able to regulate autophagy, as otherwise they might consume too much. This would result in a disrupted cellular function and ultimately in the death of the cell. To discover how cells did this, the researchers deprived the cells of food over a lengthy period. They saw that the mTOR kinase (an enzyme that provides other proteins with a phosphate group) was inhibited and at that point the cell autophagy started. When the mTOR was reactivated, this process stopped. The cell then activated mTOR using the products of autophagy, giving rise to a self-regulating system.

For autophagy, part of the cell content is first of all isolated by a membrane. The resulting autophagosome receives digestive enzymes by fusing with a lysosome that already contains these. The result is an autolysosome. The researchers observed that the cell recycles the lysosomes during autophagy and generates new lysosomes from this.


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