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Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade

Title
Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade
Authors
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
오구택
SCOPUS Author ID
오구택scopus
Issue Date
2012
Journal Title
EMBO Reports
ISSN
1469-221XJCR Link
Citation
vol. 13, no. 2, pp. 150 - 156
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.1038/embor.2011.246
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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