Fig. 1.

Five major types of PTM contributing to mitochondrial dysfunction and tissue injury in AFLD, NAFLD and acute liver damage. Alcohol, smoking, high fat diet, hepatotoxic compounds and aberrant genetic mutations can lead to increased production of ROS and RNS either individually or synergistically, leading to elevated nitroxidative stress. Under increased nitroxidative stress, many cellular (mitochondrial) proteins can be modified by different forms of PTM and inactivated, leading to mitochondrial dysfunction. Under increased mitochondrial dysfunction, greater amounts of ROS/RNS are produced while energy supply and normal metabolism can be suppressed. Accumulation of fat resulting from disrupted fat oxidation can trigger insulin resistance and lipotoxicity while protein adducts can stimulate immune responses. Sustained mitochondrial dysfunction would lead to the development of vicious cycles of PTMs and energy depletion and lipotoxicity, ultimately promoting tissue injury (necrosis/apoptosis). Many small molecule antioxidants contained in fruits and vegetables as well as exercise and calorie restrictions can be used to prevent or reduce the nitroxidative stress. Uni-directional and bi-directional arrows indicate exclusive and mutual influences (in vicious cycles), respectively.