Oxidative Stress in the Healthy and Wounded Hepatocyte: A Cellular Organelles Perspective

Figure 2

Mechanisms of enhanced ROS production during hepatocyte damage. Ethanol metabolism promotes strong ROS production in the ER by the inducible CYP. It impairs GSH import in the mitochondria, preventing ROS removal. It also impairs β-oxidation promoting lipid accumulation. ETOH induces lipid-raft clustering and increases iron uptake, promoting Fe²⁺ leakage from lysosomes and increased Fe²⁺ loads in mitochondria and ER, resulting in ROS production. Ethanol also reduced the autophagic removal of damaged cellular components. Viral infection challenges the ER protein folding process leading to ROS production and Ca²⁺ leakage in the cytosol and mitochondria. Increased MAMs formation promotes Ca²⁺ efflux from ER into mitochondria, increasing mitochondrial ROS production.