Journal
FASEB JOURNAL
Volume 30, Issue 1, Pages 66-80Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.14-268904
Keywords
cell survival; loss of mitochondria; transcription factor; mitochondrial outer membrane
Categories
Funding
- U.S. National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [R01 HL089958]
- NIH National Institute of Environmental Sciences [R21 ES017473, T32 ES007091]
- NIH National Institute of General Medicine Sciences [R01 GM111337]
- University of Arizona Sarver Heart Center Anonymous Award for Heart Failure Research
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL089958] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007091, R21ES017473] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM111337] Funding Source: NIH RePORTER
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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.-Strom, J., Xu, B., Tian, X., Chen, Q. M. Nrf2 protects mitochondrial decay by oxidative stress. FASEB J. 30, 66-80 (2016). www.fasebj.org
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