Mitochondrial function and liver health, Academician Li Lanjuan's team published the latest review

Our liver is a diligent guardian, silently breaking down the alcohol and drugs we consume, neutralizing toxins in the body, and finely regulating fat metabolism. To accomplish these arduous tasks, the liver relies on the energy source within the cell - mitochondria. These tiny "energy factories" produce ATP through the process of oxidative phosphorylation (OXPHOS), providing the necessary power for various life activities of the liver. However, once the mitochondria are damaged, the liver's work efficiency will drop significantly, which may cause a series of health problems. For example, in alcohol-related liver disease (ALD), the metabolism of alcohol produces a large number of free radicals. These highly reactive molecules attack mitochondria and hinder their normal function, thereby triggering inflammatory responses and cell damage. Similarly, in non-alcoholic fatty liver disease (NAFLD), excessive fat accumulation in the liver can also disrupt the work of mitochondria, reduce energy production, and aggravate liver damage. Mitochondrial dysfunction plays a key role in the occurrence and development of liver disease. Therefore, protecting the health of mitochondria is essential for maintaining liver function. Recently, infectious disease experts Academician Li Lanjuan and Professor Jiang Ying'an's team published a review article (Mitochondrial dysfunction: A promising therapeutic target for liver diseases) in Genes & Diseases, which deeply explored the role of mitochondrial dysfunction in liver disease and discussed a variety of potential treatment strategies.

Different types of mitochondrial dysfunction

Mitochondrial dysfunction and liver disease

The article discusses the role of mitochondria in acute liver injury and chronic liver diseases such as hepatocellular carcinoma, viral hepatitis, drug-induced liver injury, alcoholic liver disease, and non-alcoholic fatty liver disease. The mechanisms of mitochondrial dysfunction involve multiple aspects, including damage to mitochondrial DNA (mtDNA), imbalances in mitochondrial morphology and number, and reduced ATP production. Together, these processes affect liver health and function.

Impact of mitochondrial dynamic imbalance on liver health

The figure above describes the relationship between mitochondrial dynamics and liver disease. Changes in the morphology and number of mitochondria, namely mitochondrial dynamics, are crucial to the energy supply and overall health of cells. Figure (A) shows the relationship between mitochondrial dynamics and cell activity; Figures (B) and (C) detail how liver health is affected when mitochondrial dynamics are unbalanced. Mitochondrial dynamic imbalance can be likened to a malfunction in the energy transfer system inside the cell, which not only leads to energy shortages, but can also trigger inflammatory responses and cell death, thereby damaging the liver.

The role of mitochondrial biogenesis and autophagy in liver disease

Mitochondrial biogenesis and autophagy are two key mechanisms that cells use to maintain their own health. They are responsible for making new mitochondria and removing damaged ones, thereby keeping energy production in the cell running efficiently. In liver disease, these processes play a protective role. However, when these mechanisms are out of balance, they may promote liver damage and the development of cancer.

The figure above shows the role of mitochondrial biogenesis and autophagy in liver disease

How to repair these damaged mitochondria?

Antioxidant Supplementation

Antioxidants such as MitoQ, vitamin C/E, and lipoic acid can neutralize harmful free radicals produced by mitochondria, thereby reducing oxidative stress and protecting mitochondria from damage. These antioxidants not only help restore mitochondrial function, but also improve the efficiency of cellular energy metabolism and support the healthy functioning of the liver.

Mitochondrial biogenesis promotion can promote mitochondrial biogenesis and increase the number of healthy mitochondria by activating transcriptional coactivators such as PGC-1α. This approach can enhance the energy production capacity of cells, thereby improving the overall metabolic state of the liver.

Mitochondrial transplantation In addition, the article introduces the concept of mitochondrial transplantation. This is an emerging treatment strategy that involves transferring healthy mitochondria directly into damaged liver cells. This approach is equivalent to replacing a new "energy factory" for the liver and restoring its normal metabolic function. Studies have shown that by directly injecting healthy mitochondria into the liver, drug-induced liver damage can be effectively reduced and liver tissue repair and functional improvement can be promoted.

As our understanding of the relationship between mitochondrial function and liver disease deepens, more therapeutic drugs targeting mitochondria may be developed in the future. These drugs can help repair damaged mitochondria and reduce oxidative stress, thereby treating or preventing liver disease. In addition, research may also promote the development of personalized medicine by tailoring treatment plans to the individual's mitochondrial condition. We look forward to these findings being translated into clinical practice as soon as possible, bringing new hope and a better quality of life to patients with liver disease, and looking forward to a tomorrow without liver disease.

References

[1] Chen P, Yao L, Yuan M, Wang Z, Zhang Q, Jiang Y, Li L. Mitochondrial dysfunction: A promising therapeutic target for liver diseases. Genes Dis. 2023 Sep 17;11(3):101115. doi: 10.1016/j.gendis.2023.101115. PMID: 38299199; PMCID: PMC10828599.