Mitochondrial transplantation

Mitochondria generate energy by converting fatty acids and carbohydrates into carbon dioxide and water, nourishing the cells of the whole body. There is a significant association between mitochondrial damage and various liver diseases. Defective mitochondria cannot provide the liver with enough energy for normal functioning. This leads to the death of hepatocytes and liver failure.

Currently, the only way to treat liver failure is a complete organ transplant. Surgeons in the United States perform about 8,000 liver transplants a year, but due to a shortage of donor organs, thousands of people on the waiting list die without waiting in line.

A researcher from the University of Connecticut, Professor George Wu and his colleagues have shown that mitochondria can be coated with certain carrier proteins that are recognized by hepatocytes. These proteins have a carbohydrate galactose on the surface, which signals to the liver that it needs to be absorbed.

Using a normal natural mechanism, the researchers demonstrated that healthy mitochondrial complexes can be delivered to the liver of live rats with a simple intravenous injection.

The group collected mitochondria from mouse liver samples, added the carrier protein asialoorosomucoid-polylysine (AsORPL) to them and purified them to form complexes. The endosomolytic peptide listeriolysin O (LLO) was also injected into the mitochondria. Forming an AsORLLO complex with the carrier protein, it facilitated the release of mitochondria after ingestion of hepatocytes. This peptide did not allow the mitochondria to digest – the liver does this with most of the molecules it assimilates.

After intravenous injection, the liver of recipient rats was analyzed using quantitative polymerase chain reaction of mitochondrial mouse DNA, electron microscopy and in situ polymerase chain reaction and hybridization followed by immunohistochemical analysis. Wu and his colleagues found that approximately 27% of the total number of injected mitochondria reached the liver – a high result for possible therapeutic use.

Less than 2% of donor mitochondria were found in the spleen and less than 1% in the lungs, which proves that accumulation in the liver is not accidental and absorption was not evenly distributed throughout all organs. In other words, the protein coating created by the researchers made the donor mitochondria specifically identifiable and assimilated by the liver.

This is also an important achievement because mitochondria usually die in the bloodstream when they come into contact with blood cells, blood proteins, narrow blood vessels and from attacks from the immune system.

While the experiment evaluated only the short-term effects of mitochondrial transplantation, there are potential long-term prospects. Mitochondria have their own DNA and RNA, so they can reproduce independently of the rest of the cell. Transplanted mitochondria can replicate with cells during cell division. Cells updated in this way can gradually eliminate damaged mitochondria, the number of healthy donor mitochondria will increase until it reaches the required level.

The next stage of the group plans to test the method on rats with mitochondrial liver damage. This will show the potential clinical significance of the method for the treatment of liver pathologies and mitochondrial diseases of other organs.

The method of targeted transplantation of mitochondria into hepatocytes is patented by the authors.

Article X.Liu et al. Targeted delivery of mitochondria to the liver in rats is published in the Journal of Gastroenterology and Hepatology.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on UCONN materials: UConn Professor Successfully Demonstrates Delivery of Microscopic Powerhouses to Liver in Animals.