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        Emerging evidence for crosstalk between Nrf3 and mitochondria in physiological homeostasis and in heart disease

        Michiko Tsushima,Jun Liu,Wataru Hirao,Hiromi Yamazaki,Hirofumi Tomita,Ken Itoh 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.3

        Nrf2 regulates redox homeostasis in cells bycoordinately regulating a range of antioxidant enzymes andproteins. An increase in oxidative stress is one of the hallmarksof aging, and Nrf2 protein levels and activity decreasewith aging. Decreased mitochondrial functions, such asdecreased ATP production, also occur with aging, leadingto the increased generation of reactive oxygen species (ROS)and oxidative stress. Thus, understanding the relationshipsbetween Nrf2 and the mitochondria is important for clarifyingthe regulatory mechanisms of aging. It is becomingclear that Nrf2 is activated in a tissue-specific manner inresponse to mitochondrial or NADPH oxidase-generatedROS. As the heart consists of postmitotic cells that utilizeATP produced mainly by mitochondrial oxidative phosphorylation,cardiomyocytes are equipped with highly sophisticatedmitochondrial quality control mechanisms. Consistentwith these findings, it has been reported that Nrf2 inthe heart is regulated via a specific translational mechanismand that Nrf2 activation confers cardioprotective effects invarious disease models. Thus, Nrf2 is a promising target foranti-aging strategies to combat age-related heart diseases,such as age-related cardiomyopathy.

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