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Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade
- Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade
- Kwon J.; Han E.; Bui C.-B.; Shin W.; Lee J.; Lee S.; Choi Y.-B.; Lee A.-H.; Lee K.-H.; Park C.; Obin M.S.; Park S.K.; Seo Y.J.; Oh G.T.; Lee H.-W.; Shin J.
- Ewha Authors
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- EMBO Reports
- vol. 13, no. 2, pp. 150 - 156
- SCI; SCIE; SCOPUS
- Sqstm1/p62 functions in the non-canonical activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, its physiological relevance is not certain. Here, we show that p62 -/- mice exhibited an accelerated presentation of ageing phenotypes, and tissues from these mice created a pro-oxidative environment owing to compromised mitochondrial electron transport. Accordingly, mitochondrial function rapidly declined with age in p62 -/- mice. In addition, p62 enhanced basal Nrf2 activity, conferring a higher steady-state expression of NAD(P)H dehydrogenase, quinone 1 (Nqo1) to maintain mitochondrial membrane potential and, thereby, restrict excess oxidant generation. Together, the p62-Nrf2-Nqo1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity. © 2012 european molecular biology organization.
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