| First Author | Kwon J | Year | 2012 |
| Journal | EMBO Rep | Volume | 13 |
| Issue | 2 | Pages | 150-6 |
| PubMed ID | 22222206 | Mgi Jnum | J:181228 |
| Mgi Id | MGI:5309093 | Doi | 10.1038/embor.2011.246 |
| Citation | Kwon J, et al. (2012) Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade. EMBO Rep 13(2):150-6 |
| abstractText | 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. |
