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


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.

DOI: 10.1038/embor.2011.246

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@article{Kwon2012AssuranceOM, title={Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade.}, author={Jeongho Kwon and Eunhye Han and Chi-Bao Bui and Woochul Shin and Junho Lee and Sejeong Lee and Young-Bong Choi and Ann-Hwee Lee and Kyong-Hoon Lee and Chankyu Park and Martin S Obin and Sung Kyu Park and Yun Jeong Seo and Goo Taeg Oh and Han-Woong Lee and Jaekyoon Shin}, journal={EMBO reports}, year={2012}, volume={13 2}, pages={150-6} }