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 journalArticle

75 Citations (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.

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

Fingerprint

NAD(P)H Dehydrogenase (Quinone)
Mitochondrial Membrane Potential
Electron Transport
Oxidants
Aging of materials
Chemical activation
Tissue
Membranes
Phenotype

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Kwon, J., Han, E., Bui, C. B., Shin, W., Lee, J., Lee, S., ... Shin, J. (2012). Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade. EMBO Reports, 13(2), 150-156. https://doi.org/10.1038/embor.2011.246
Kwon, Jeongho ; Han, Eunhye ; Bui, Chi Bao ; Shin, Woochul ; Lee, Junho ; Lee, Sejeong ; Choi, Young Bong ; Lee, Ann Hwee ; Lee, Kyong Hoon ; Park, Chankyu ; Obin, Martin S. ; Park, Sung Kyu ; Seo, Yun Jeong ; Oh, Goo Taeg ; Lee, Han Woong ; Shin, Jaekyoon. / Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade. In: EMBO Reports. 2012 ; Vol. 13, No. 2. pp. 150-156.
@article{2864a1a3d97648eea3ccb71cb1be8d0a,
title = "Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade",
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.",
author = "Jeongho Kwon and Eunhye Han and Bui, {Chi Bao} and Woochul Shin and Junho Lee and Sejeong Lee and Choi, {Young Bong} and Lee, {Ann Hwee} and Lee, {Kyong Hoon} and Chankyu Park and Obin, {Martin S.} and Park, {Sung Kyu} and Seo, {Yun Jeong} and Oh, {Goo Taeg} and Lee, {Han Woong} and Jaekyoon Shin",
year = "2012",
month = "1",
day = "1",
doi = "10.1038/embor.2011.246",
language = "English",
volume = "13",
pages = "150--156",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "2",

}

Kwon, J, Han, E, Bui, CB, Shin, W, Lee, J, Lee, S, Choi, YB, Lee, AH, Lee, KH, Park, C, Obin, MS, Park, SK, Seo, YJ, Oh, GT, Lee, HW & Shin, J 2012, 'Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade', EMBO Reports, vol. 13, no. 2, pp. 150-156. https://doi.org/10.1038/embor.2011.246

Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade. / Kwon, Jeongho; Han, Eunhye; Bui, Chi Bao; Shin, Woochul; Lee, Junho; Lee, Sejeong; Choi, Young Bong; Lee, Ann Hwee; Lee, Kyong Hoon; Park, Chankyu; Obin, Martin S.; Park, Sung Kyu; Seo, Yun Jeong; Oh, Goo Taeg; Lee, Han Woong; Shin, Jaekyoon.

In: EMBO Reports, Vol. 13, No. 2, 01.01.2012, p. 150-156.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade

AU - Kwon, Jeongho

AU - Han, Eunhye

AU - Bui, Chi Bao

AU - Shin, Woochul

AU - Lee, Junho

AU - Lee, Sejeong

AU - Choi, Young Bong

AU - Lee, Ann Hwee

AU - Lee, Kyong Hoon

AU - Park, Chankyu

AU - Obin, Martin S.

AU - Park, Sung Kyu

AU - Seo, Yun Jeong

AU - Oh, Goo Taeg

AU - Lee, Han Woong

AU - Shin, Jaekyoon

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863041323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863041323&partnerID=8YFLogxK

U2 - 10.1038/embor.2011.246

DO - 10.1038/embor.2011.246

M3 - Article

VL - 13

SP - 150

EP - 156

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 2

ER -