The many roles of Nrf2 in mitochondrial function


The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the master regulator of the cellular redox homeostasis. Nrf2 target genes include a massive system of antioxidant enzymes, proteins involved in xenobiotic detoxification, removal and repair of damaged proteins, inhibition of inflammation, in addition to other transcription factors. In the past few years it has surfaced that within its function as a regulator of cytoprotective gene expression, Nrf2 impacts adrenal function. Greater Nrf2 activity defends against mitochondrial toxins. Reduced glutathione, the primary little molecule antioxidant in the squamous cell along with a product of a number of the downstream target genes of Nrf2, counterbalances mitochondrial ROS production. The use of Nrf2 is curbed in mitochondria-related ailments, such as Parkinson’s disease and Friedrich’s ataxia. Studies with isolated mitochondria and endothelial cells have shown that Nrf2 deficiency contributes to impaired mitochondrial fatty acid oxidation, respiration and ATP production. Small molecule activators of Nrf2 support mitochondrial integrity by boosting mitophagy and conferring resistance to cognitive stress-mediated permeability transition. Excitingly, recent studies have proven that Nrf2 additionally affects mitochondrial role in stem cells with implications for stem cell self-renewal, cardiomyocyte regeneration, and neurological stem/progenitor cell survival.

Details: Glucoraphanin; Keap1; Mitohormesis; Mitophagy; Neurodegenerative disorder; Nrf; PMI; RTA-408; Stem cells; Sulforaphane.

Source: https://pubmed.ncbi.nlm.nih.gov/28066829/

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