Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications

Mammalians are constantly exposed to exogenous and endogenous sources of free radicals that have both favorable and harmful effects on the cellular systems. Oxidative stress (OS) is an imbalance of reactive oxygen species (ROS) and antioxidants in the body that can lead to serious cell damage. It is associated with many diseases such as cancer, Alzheimer’s disease and heart disease. Background/Objectives: The Nuclear factor-2 erythroid-related factor-2 (Nrf2) is a transcription factor that controls the cellular oxidation state using antioxidant systems in the body and affects mitochondrial activities. Increased Nrf2 levels serve to protect cells from mitochondrial toxins; however, Nrf2 activity is inhibited in mitochondria-related diseases. In addition, Nrf2 is involved in mitochondrial activities for OS control. Methods: As mitochondrial wellbeing and activity is the chief controller for cellular metabolism, Nrf2 is a critical regulator for metabolic pathways. Thus, Nrf2 is the chief organizer of protection against OS in the cells. Nrf2 activator molecules support mitochondrial activity by stimulating mitophagy and helping to battle OS-related permeability transition. Conclusions: This review describes the influence of Nrf2 on OS and the way Nrf2 modulates mitochondrial function. Furthermore, we highlight recent studies of Nrf2 regarding its possible role in cell systems as well as pharmacological implications. Furthermore, this review emphasizes the importance of the mitochondria in the development of life-threatening diseases; pharmacological activation of Nrf2 is an important strategy to counter mitochondrial dysfunction