Cited by 783Redox biology and oxidative stressMitochondrial Function and PathologyNitric Oxide and Endothelin Effects

Cross talk between mitochondria and NADPH oxidases

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Dikalov, Sergey·2011·Free Radical Biology and Medicine

Abstract

Reactive oxygen species (ROS) play an important role in physiological and pathological processes. In recent years, a feed-forward regulation of the ROS sources has been reported. The interactions between the main cellular sources of ROS, such as mitochondria and NADPH oxidases, however, remain obscure. This work summarizes the latest findings on the role of cross talk between mitochondria and NADPH oxidases in pathophysiological processes. Mitochondria have the highest levels of antioxidants in the cell and play an important role in the maintenance of cellular redox status, thereby acting as an ROS and redox sink and limiting NADPH oxidase activity. Mitochondria, however, are not only a target for ROS produced by NADPH oxidase but also a significant source of ROS, which under certain conditions may stimulate NADPH oxidases. This cross talk between mitochondria and NADPH oxidases, therefore, may represent a feed-forward vicious cycle of ROS production, which can be pharmacologically targeted under conditions of oxidative stress. It has been demonstrated that mitochondria-targeted antioxidants break this vicious cycle, inhibiting ROS production by mitochondria and reducing NADPH oxidase activity. This may provide a novel strategy for treatment of many pathological conditions including aging, atherosclerosis, diabetes, hypertension, and degenerative neurological disorders in which mitochondrial oxidative stress seems to play a role. It is conceivable that the use of mitochondria-targeted treatments would be effective in these conditions.

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Authors
Dikalov, S.
Affiliations
Emory University (US)
Corresponding author
Dikalov, Sergey
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2011-10
Volume
51
Issue
7
Pages
1289-1301
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2011124873
Cited by
783
References
186
Citations by year
2026: 26 · 2025: 31 · 2024: 35 · 2023: 51 · 2022: 54 · 2021: 59 · 2020: 69 · 2019: 53 · 2018: 62 · 2017: 70 · 2016: 50 · 2015: 63 · 2014: 59 · 2013: 60 · 2012: 39
FWCI
4.64
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL094469, HL094469)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
mitochondria, NADPH oxidase, reactive oxygen species, mitochondrial ROS production, feedforward control, oxidative stress, mitochondria-targeted antioxidants, redox state, mitochondrial dysfunction, aging, atherosclerosis, diabetes mellitus, hypertension, degenerative neurological disorders
MeSH terms
Aging, Angiotensin II, Animals, Antioxidants, Diabetes Mellitus, Humans, Hypertension, Mitochondria, Organophosphorus Compounds, Oxidation-Reduction, Piperidines, Rabbits, Superoxide Dismutase, Xanthine Oxidase, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Neurodegenerative Diseases, Atherosclerosis, Mice, Rats, Nitric Oxide Synthase Type III

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