Research Uncovers Potential Remedy for Alcohol-Related Liver Disease
Medical researchers at Cedars-Sinai have discovered a new method that illustrates how increased alcohol consumption leads to liver damage, specifically mitochondrial dysfunction, potentially leading to new treatments for people afflicted with alcohol-related liver disease (ARLD).
ARLD cases are on the rise and represent one of the leading causes of alcohol-related fatalities, including diseases such as hepatitis, fibrosis, cirrhosis, and liver cancer.
Cirrhosis accounts for 1.6 million deaths globally, with more than half of those fatalities resulting from alcohol abuse, and there are no effective treatments besides abstinence.
Shelly C. Lu, MD, stated that ARLD is a major global concern; she also noted that the association between mitochondrial damage and alcohol consumption had been known for a long time, but the mechanisms that determine this damage have not been clear until now.
Mitochondria, the cell's powerhouse, play a vital role in the liver's function; however, alcohol abuse can disrupt their structure and processes leading to organ damage.
Cedars-Sinai Study Results
Dr. Lu and her team analyzed the role of the MATα1 enzyme that provides nutrients to the liver and have found that the enzyme was selectively reduced in preclinical models and liver tissues from patients affected by ARLD.
- Their research uncovered that alcohol activated a protein called casein kinase 2 (CK2), triggering the phosphorylation of MATα1, which facilitated interaction with the PIN1 protein and prevented MATα1 from transporting essential nutrients into the mitochondria.
- Knowing this, the team decided to mutate MATα1 to disable interaction with PIN1 and prevent phosphorylation, preserving mitochondrial MATα1 location and function and preventing mitochondrial damage from alcohol consumption. A similar result was apparent when they reduced CK2 expression.
- According to Dr. Lu and her team, these results support a novel and targetable mechanism to help treat ARLD. They aim to develop small molecule therapeutics that can disrupt MATα1 and PIN1 interactions, the goal being to protect mitochondria from damage as a result of alcohol consumption.
Additional Cedars-Sinai co-authors of the study include Ben Murray, Jin Won Yang, Jiaohong Wang, Michitaka Matsuda, Wei Fan, Nirmala Mavila, Hui Peng, Komal Ramani, Ekihiro Seki and Jennifer Van Eyk.