The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases

• Published in: Antioxidants Vol. 12; no. 11; p. 1928
• Main Authors: Park, Jeong-Su, Rustamov, Nodir, Roh, Yoon-Seok
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2023
• Subjects: Alcohol; Antioxidants; Autophagy; By products; CLD; Cytochrome; Cytokines; Defense mechanisms; Development and progression; Enzymes; Ethanol; Fatty acids; Fatty liver; Fibrosis; Free radicals; Genes; Gluconeogenesis; Health aspects; Heme; Hepatotoxicity; Homeostasis; Hydrogen peroxide; Inflammation; Lipid peroxidation; Lipids; Liver cancer; Liver cirrhosis; Liver diseases; Metabolism; Mitochondria; NRF2; Oxidative stress; Physiological aspects; Prevention; Quality control; Quality management; Reactive oxygen species; ROS
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox12111928

Chronic liver disease (CLD) affects a significant portion of the global population, leading to a substantial number of deaths each year. Distinct forms like non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central to liver metabolism, mitochondria are essential for ATP production, gluconeogenesis, fatty acid oxidation, and heme synthesis. However, in diseases like NAFLD, ALD, and liver fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, and metabolic irregularities. This dysfunction, especially electron leakage, exacerbates the production of reactive oxygen species (ROS), augmenting liver damage. Amidst this, nuclear factor erythroid 2-related factor 2 (NRF2) emerges as a cellular protector. It not only counters oxidative stress by regulating antioxidant genes but also maintains mitochondrial health by overseeing autophagy and biogenesis. The synergy between NRF2 modulation and mitochondrial function introduces new therapeutic potentials for CLD, focusing on preserving mitochondrial integrity against oxidative threats. This review delves into the intricate role of oxidative stress in CLD, shedding light on innovative strategies for its prevention and treatment, especially through the modulation of the NRF2 and mitochondrial pathways.