Mito!! Give me the power to rejuvenate!
Mitochondria are the powerhouse of cells - have been inscribed in our mind since school. However, we do not know their involvement in liver regeneration. Scientists at UT Southwestern Medical Center determined that liver cells with damaged mitochondria cannot regenerate when injured, thereby allowing cells with undamaged mitochondria to grow and rejuvenate the liver. This study was published in the Science journal’s June 2024 issue.
Mitochondria are the powerhouse of cells - have been inscribed in our mind since school. However, we do not know their involvement in liver regeneration. Scientists at UT Southwestern Medical Center determined that liver cells with damaged mitochondria cannot regenerate when injured, thereby allowing cells with undamaged mitochondria to grow and rejuvenate the liver. This study was published in the Science journal’s June 2024 issue.
According to the CDC (Centers for Disease Control and Prevention), liver disease is the 10th leading cause of death in the United States. Liver diseases such as liver failure, cancer, and fatty liver cause the liver to lose its regeneration capacity. Past studies have shown that damaged mitochondria accumulate in liver cells in these diseases. This motivated the scientists to find out how damaged mitochondria could affect liver regeneration. The scientists used a mouse model to surgically remove 70% of the liver, forcing it to regenerate. During regeneration, they observed lower fatty acid levels due to increased fatty acid digestion in the mitochondria of liver cells. They confirmed these findings by damaging the mitochondria, thus reducing the digestion, and observed increased fatty acid levels. Consequently, the liver regeneration was decreased. They rescued the regeneration by using chemical/genetic manipulation to increase fatty acid digestion and reduce fatty acid levels in the damaged mitochondria, thereby validating the role of fatty acids in liver regeneration. Based on these findings, they concluded that damaged mitochondria reduced liver regeneration due to increased fatty acid, allowing cells with healthy mitochondria to grow, contributing to regeneration. This is a good example of natural selection at a cellular level to promote a healthy organ.
What are the next steps?
This study demonstrated that decreasing fatty acid levels in damaged mitochondria improves mice’s liver regeneration ability. The next step would be to test this in liver disease models in other large animals or organ-on-chip. The ultimate test would be in clinical trials to know their efficacy and safety in humans. However, getting approval for clinical trials is a long process with multiple steps that could take several years.
How does this research affect humans?
In liver diseases, where most of the mitochondria are damaged, the liver is unable to rejuvenate. According to this study, it could be treated by therapies that decrease fatty acid levels. However, patients with liver diseases have different underlying causes. These therapies could work only on those patients who have high fatty acid levels in their liver cells’ mitochondria. Thus, to determine who would respond to these drugs, patients’ biopsies need to be performed to measure mitochondrial fatty acid levels. This study opens new directions to treat liver diseases, whose potential needs to be further verified.
More detail
The research article was published in the Science journal on June 14th, 2024, and is available at the following link.