Nrf2 protects mitochondrial decay by oxidative stress

Joshua Strom, Beibei Xu, Xiuqing Tian, Qin Chen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Sublethal levels of oxidative stress are commonly associated with various pathophysiological conditions. Cardiomyocytes have the highest content of mitochondria among all cell types, allowing the study of mitochondria in cells surviving oxidative stress and address whether nuclear factor-erythroid-derived 2-related factor 2 (Nrf2) can reverse these changes. Mitochondria normally exist in elaborated networks, which were replaced by predominately individual punctuate mitochondria 24 h after exposure to a nonlethal dose of H2O2. Electron microscopy revealed that cells surviving H2O2 show swelling of mitochondria with disorganized cristae and areas of condensation. Measurements of functional mitochondria showed a H2O2 dose-dependent decrease over a course of 5 d. At the protein and mRNA levels, cells surviving H2O2 treatment show a reduction of mitochondrial components, cytochrome c, and cytochrome b. Nrf2 overexpression prevented H2O2 from inducing mitochondria morphologic changes and reduction of cytochrome b/c. Although Nrf2 is known as a transcription factor regulating antioxidant and detoxification genes, Nrf2 overexpression did not significantly reduce the level of protein oxidation. Instead, Nrf2 was found to associate with the outer mitochondrial membrane. Mitochondria prepared from the myocardium of Nrf2 knockout mice are more sensitive to permeability transition. Our data suggest that Nrf2 protects mitochondria from oxidant injury likely through direct interaction with mitochondria.

Original languageEnglish (US)
Pages (from-to)66-80
Number of pages15
JournalFASEB Journal
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2016

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Mitochondria
Oxidative stress
Oxidative Stress
Cytochromes b
Detoxification
Mitochondrial Membranes
Cytochromes c
Cardiac Myocytes
Oxidants
Knockout Mice
Electron microscopy
Swelling
Condensation
Permeability
Myocardium
Electron Microscopy
Proteins
Transcription Factors
Antioxidants
Genes

Keywords

  • Cell survival
  • Loss of mitochondria
  • Mitochondrial outer membrane
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Nrf2 protects mitochondrial decay by oxidative stress. / Strom, Joshua; Xu, Beibei; Tian, Xiuqing; Chen, Qin.

In: FASEB Journal, Vol. 30, No. 1, 01.01.2016, p. 66-80.

Research output: Contribution to journalArticle

Strom, Joshua ; Xu, Beibei ; Tian, Xiuqing ; Chen, Qin. / Nrf2 protects mitochondrial decay by oxidative stress. In: FASEB Journal. 2016 ; Vol. 30, No. 1. pp. 66-80.
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