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Semin Liver Dis
DOI: 10.1055/a-2421-5658
Review Article

Mitochondria and Alcohol-Associated Liver Disease: Pathogenic Role and Target for Therapy

Sandra Torres
1   Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Unidad Associada IMIM/IIBB-CSIC, Barcelona, Spain
2   Liver Unit, Hospital Clinic i Provincial de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3   Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
,
Josiah Hardesty
4   Division of Gastroenterology and Hepatology, University of Louisville, Louisville, Kentucky
5   Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, Kentucky
,
Monica Barrios
1   Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Unidad Associada IMIM/IIBB-CSIC, Barcelona, Spain
2   Liver Unit, Hospital Clinic i Provincial de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3   Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
,
Carmen Garcia-Ruiz
1   Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Unidad Associada IMIM/IIBB-CSIC, Barcelona, Spain
2   Liver Unit, Hospital Clinic i Provincial de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3   Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
,
Jose C. Fernandez-Checa
1   Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Unidad Associada IMIM/IIBB-CSIC, Barcelona, Spain
1   Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Unidad Associada IMIM/IIBB-CSIC, Barcelona, Spain
2   Liver Unit, Hospital Clinic i Provincial de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3   Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
6   Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
,
Ashwani K. Singal
1   Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Unidad Associada IMIM/IIBB-CSIC, Barcelona, Spain
4   Division of Gastroenterology and Hepatology, University of Louisville, Louisville, Kentucky
7   Transplant Hepatology, Trager Transplant Center and Jewish Hospital, University of Health, Louisville, Kentucky
8   Department of Clinical Research, Robley Rex VA Medical Center, Louisville, Kentucky
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Abstract

Alcohol-associated liver disease (ALD) is one of the leading causes of chronic liver disease and a major cause of liver-related death. ALD is a multifactorial disease triggered by the oxidative metabolism of alcohol which leads to the activation of multiple factors that promote the progression from steatosis to more advanced stages like alcohol-associated steatohepatitis (AH) that culminate in alcohol-associated cirrhosis and hepatocellular carcinoma. Poor understanding of the complex heterogeneous pathology of ALD has limited drug development for this disease. Alterations in mitochondrial performance are considered a crucial event in paving the progression of ALD due to the crucial role of mitochondria in energy production, intermediate metabolism, calcium homeostasis, and cell fate decisions. Therefore, understanding the role of mitochondria in eliciting steatosis and progression toward AH may open the door to new opportunities for treatment. In this review, we will cover the physiological function of mitochondria, its contribution to ALD in experimental models and human disease, and explore whether targeting mitochondria may represent a game changer in the treatment of ALD.

Keywords

bioenergetics - antioxidants - oxidative stress - ROS


Publication History

Accepted Manuscript online:
24 September 2024

Article published online:
21 October 2024

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