In search of a panacea
One enzyme plays a key role in the development of cancer, diabetes and Parkinson's disease
Svetlana Maslova, Hi-tech+
The discovery of American researchers indicates new opportunities in the treatment of all three diseases, and possibly more. They managed to uncover the general mechanism of cell purification from defective mitochondria, which without proper "cleaning" lead to the development of many serious diseases.
The work of a team from the Salk Institute for Biological Research has shown that the mechanisms underlying the well-being of body cells are much more integrated than previously thought. It turned out that the enzyme, which plays a crucial role in the development of cancer and type 2 diabetes, also activates the "cleansing" protein parkin in Parkinson's disease.
Article by Hung et al. AMPK/ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy published in the journal Science Advances – VM.
When cells are stressed, certain chemical signals are triggered that protect the most important components of the cell. For example, the parkin protein in such conditions is in a hurry to protect mitochondria. Experiments have shown that there is a direct relationship between the main sensor of cellular stress and parkin.
"Our results represent the earliest processes triggered in response to Parkin's signals. All other known biochemical events occur within an hour. We have opened a path that activates within five minutes," said the author of the work Ruben Shaw.
The discovery of this mechanism is very important, because deciphering this step, during which cells get rid of defective mitochondria, affects a number of diseases, the scientist added.
For example, Parkin's role in clearing defective mitochondria damaged by cellular stress (a process called mitophagy) was known, but how exactly Parkin identified problems with mitochondria was still unknown.
To find out, the team turned to the results of their earlier discovery. About ten years ago, they determined that the AMPK enzyme controls autophagy (the process of recycling cell components) through the activation of the ULK1 enzyme. They began searching for autophagy-related proteins directly activated by ULK1.
The researchers were extremely surprised to find only three proteins – first AMPK, then ULK1 and then parkin, which trigger such an important process.
The results have very different consequences, since each of the three participants plays a role in the development of cancer, diabetes, Parkinson's disease and other neurodegenerative diseases or responds in a specific way to drugs.
"The main conclusion for me is that metabolism and changes in the state of mitochondria are crucial in cancer and are very critical in the development of diabetes and neurodegenerative diseases," said Shaw. Now his team intends to study in more detail the effect of this mechanism on the development of diseases, as well as to test the effect of certain drugs. For example, they plan to evaluate the effect of metformin activating AMPK for the therapy of neurodegenerative diseases. Previously, it has already shown effectiveness in suppressing the growth of cancer.
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