September 25, 2022

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This is how cells repair their ‘incinerators’

Discover the mechanism by which cells repair “incinerators,” or lysosomes, the organelles that break down and recycle waste, counteracting aging. The discovery, which may have implications for fighting diseases such as Alzheimer’s, was published in the journal Nature by researchers at the University of Pittsburgh in the US.

“Particle damage is a hallmark of aging and many diseases, especially neurodegenerative diseases such as Alzheimer’s,” says the study’s first author, Gai Xiaojun Tan. “Our work identifies a number of steps that we believe constitute a global mechanism of lysosomal repair.”

Inside these organelles contain powerful digestive enzymes that break down cellular waste and for this reason they are isolated from the rest of the cell by a strong membrane that acts as a barrier: if damage occurs and the contents leak out, the cell immediately activates a contingency plan, the researchers note that it survives after lysosomal injury The deliberate intention of some cells grown in the laboratory.

After a few minutes of damage, the enzyme PI4K2A immediately kicks in, setting off the alarm by producing high levels of a signaling molecule called PtdIns4P. This type of red flag calls on the ORP proteins, which surround the region to be secured: they do so by binding on the one hand the PtdIns4P molecule located on the lysosome, and on the other the endoplasmic reticulum, a cellular structure involved in the synthesis. of proteins and fats. In practice, the endoplasmic reticulum wraps itself around the lysosome like an endosome and through this close contact, substances needed to repair the damage, such as cholesterol and the lipid phosphatidylserine, are transferred to the lysosome.

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Researchers believe that this mechanism is sufficient in healthy people to quickly repair small damage to the lysosomal membrane. However, when the lesion is very large or the repair mechanism is compromised (due to aging or disease), there can be leakage of dangerous substances, such as tau protein fibers that contribute to the development of Alzheimer’s disease: the researchers demonstrated this simply by eliminating the PI4K2A enzyme. The next goal will be to try to understand in an animal model whether the newly discovered lysosomal repair mechanism could play a role in preventing Alzheimer’s disease.

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