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

Jeongho Kwon, Eunhye Han, Chi Bao Bui, Woochul Shin, Junho Lee, Sejeong Lee, Young Bong Choi, Ann Hwee Lee, Kyong Hoon Lee, Chankyu Park, Martin S. Obin, Sung Kyu Park, Yun Jeong Seo, Goo Taeg Oh, Han Woong Lee, Jaekyoon Shin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalEMBO Reports
Volume13
Issue number2
DOIs
StatePublished - Jan 1 2012

Keywords

  • mammalian longevity
  • mitochondria
  • nqo1
  • nrf2
  • p62

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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