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Emerging evidence for crosstalk between Nrf2 and mitochondria in physiological homeostasis and in heart disease

Archives of Pharmacal Research 2020년 43권 3호 p.286 ~ 296
Tsushima Michiko, Liu Jun, Hirao Wataru, Yamazaki Hiromi, Tomita Hirofumi, Itoh Ken,
소속 상세정보
 ( Tsushima Michiko ) - Hirosaki University Graduate School of Medicine Department of Stress Response Science
 ( Liu Jun ) - Hirosaki University Graduate School of Medicine Department of Stress Response Science
 ( Hirao Wataru ) - Hirosaki University Graduate School of Medicine Department of Stress Response Science
 ( Yamazaki Hiromi ) - Hirosaki University Graduate School of Medicine Department of Stress Response Science
 ( Tomita Hirofumi ) - Hirosaki University Graduate School of Medicine Department of Cardiology and Nephrology
 ( Itoh Ken ) - Hirosaki University Graduate School of Medicine Department of Stress Response Science

Abstract


Nrf2 regulates redox homeostasis in cells by coordinately regulating a range of antioxidant enzymes and proteins. An increase in oxidative stress is one of the hallmarks of aging, and Nrf2 protein levels and activity decrease with aging. Decreased mitochondrial functions, such as decreased ATP production, also occur with aging, leading to the increased generation of reactive oxygen species (ROS) and oxidative stress. Thus, understanding the relationships between Nrf2 and the mitochondria is important for clarifying the regulatory mechanisms of aging. It is becoming clear that Nrf2 is activated in a tissue-specific manner in response to mitochondrial or NADPH oxidase-generated ROS. As the heart consists of postmitotic cells that utilize ATP produced mainly by mitochondrial oxidative phosphorylation, cardiomyocytes are equipped with highly sophisticated mitochondrial quality control mechanisms. Consistent with these findings, it has been reported that Nrf2 in the heart is regulated via a specific translational mechanism and that Nrf2 activation confers cardioprotective effects in various disease models. Thus, Nrf2 is a promising target for anti-aging strategies to combat age-related heart diseases, such as age-related cardiomyopathy.

키워드

Nrf2; Mitocondria; Reactive oxygen species; Mitohormesis; Heart

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