Found a New Clue for Treatment of Alcoholic Liver Disease

Korea Research Foundation, Professor Inseong Lee's Research Team at Kyungpook National University
Identifies Cause of Intracellular Mitochondrial Dysfunction

Domestic researchers have identified target factors and the pathogenesis mechanism that can effectively treat alcoholic liver disease.

The National Research Foundation of Korea announced on the 3rd that Professor In-Kyu Lee's research team at Kyungpook National University has elucidated the cause of mitochondrial dysfunction related to the onset of alcoholic liver disease, laying the foundation for developing new treatments.

Mitochondria are intracellular organelles that play a crucial role in cellular metabolism. Recently, mitochondrial dysfunction has been identified as a cause of metabolic diseases in modern people, and research on related therapeutic mechanisms is ongoing. Alcoholic liver disease is the most common liver disease worldwide, with a high mortality rate and no fundamental treatment, often requiring liver transplantation as the final treatment. Excessive alcohol intake rapidly increases the calcium concentration in mitochondria within liver cells, causing severe damage to hepatocytes.

Recently, studies on the interaction between mitochondria and intracellular organelles such as the endoplasmic reticulum, which are related to mitochondrial dysfunction and calcium accumulation in alcoholic liver disease, have attracted attention. However, the direct mechanism inducing mitochondrial calcium accumulation has not been identified, and there are limitations in developing therapies that understand and utilize this mechanism.

The research team studied the molecular mechanism causing mitochondrial dysfunction in alcoholic liver disease. They confirmed that alcohol intake increases pyruvate dehydrogenase kinase 4 (PDK4), an enzyme in mitochondria, in liver cells and promotes the formation of mitochondria-endoplasmic reticulum contacts, accelerating calcium transfer to mitochondria. This result was also confirmed through analysis of liver tissues from patients with alcoholic liver disease. In mouse models, they found that increased PDK4 enhances the formation of mitochondria-related endoplasmic reticulum calcium channeling complexes in hepatocytes and promotes mitochondrial dysfunction. Conversely, the team demonstrated that inhibiting PDK4 can prevent alcohol-induced mitochondrial calcium accumulation and functional decline.

Professor Lee explained, "By studying the mechanism of alcoholic liver disease, we identified the role of PDK4 and mitochondria-endoplasmic reticulum coupling, revealing a new therapeutic target," and added, "We will focus on developing effective and safe treatments for alcoholic liver disease through PDK4 inhibitor development."

The results of this study were published on March 27 in the international journal Nature Communications.

This content was produced with the assistance of AI translation services.