Cirrhosis and mitochondria

Scientists have uncovered the mechanism of liver damage by alcohol

Svetlana Maslova, Hi-tech+

American scientists have uncovered the mechanism of alcohol damage to the liver, which is based on mitochondrial dysfunction. This discovery will help to find ways to treat chronic diseases that lead to cirrhosis and liver cancer. In preclinical experiments, the first results of treatment look promising.

Alcohol is harmful to health and drinking a lot of alcohol, first of all, harms the liver. Now scientists from Cedars-Sinai Medical Center have demonstrated the mechanism of this process. They showed that liver damage is caused by mitochondrial dysfunction.

Article by Barbier-Torres et al. Depletion of mitochondrial methionine adenosyltransferase α1 triggers mitochondrial dysfunction in alcohol-associated liver disease published in the journal Nature Communications – VM.

"Alcohol-related liver diseases are a serious problem in the world. We have known for a long time that alcohol damages mitochondria in some way, but until now it was not clear what the mechanisms of this damage are," commented co-author Shelly Lu. To uncover these details, scientists focused on studying the enzyme MATa1, which plays a critical role for liver function. Experiments on animal models and human cell cultures have shown that MATa1 levels selectively decrease in mitochondria.

It turned out that alcohol activated the CK2 protein, which by a cascade reaction prevented the transport of MATa1 into mitochondria using the PIN1 protein. As soon as this pathway is blocked, the cells stop receiving the necessary nutrients, the scientists explain.

In subsequent experiments, they managed to block the interaction with PIN1, but retain the MATa1 function. Even when exposed to alcohol, the mitochondria were protected from damage.

Now scientists intend to develop low-molecular therapeutic agents that would be promising for the treatment of alcohol-related liver diseases in humans. In the future, their campaign opens up opportunities for the treatment of, for example, cirrhosis of the liver — the cause of 1.6 million deaths annually and the main risk factor for liver cancer.

In another study, scientists have shown that mitochondrial dysfunction can provoke the development of Alzheimer's disease — the most common neurodegenerative disease, which is also incurable.

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