Mitochondrial H + Leak and ROS Generation: An Odd Couple
Abstract
The single-electron chemistry of mitochondrial oxidative phosphorylation (ox-phos) by default generates reactive oxygen species (ROS). These ROS have roles in both physiologic cell signaling and numerous pathologic situations. One factor that has the potential to regulate ROS generation is the mild uncoupling of ox-phos, i.e., proton (H(+)) leak across the mitochondrial inner membrane. Proton leak has been shown to decrease ROS generation, whereas ROS have been shown to induce H(+) leak, and this suggests the existence of a feedback loop between ROS and H(+) leak. Interestingly, although H(+) leak is detrimental to ATP synthesis, it has been shown to be cytoprotective in several models of ischemic injury. Herein the molecular basis of both ROS generation and H(+) leak will be reviewed and the consequences of their interaction for mitochondrial function discussed.
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In the presence of these inhibitors, the highly reduced state of components of the electron transport system causes a rise in the production of superoxide at these sites, which would be a challenge to cell survival.
“In the presence of these inhibitors, the highly reduced state of components of the electron transport system causes a rise in the production of superoxide at these sites [47,48], which would be a challenge to cell survival.”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [47]
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- Authors
- Brookes, P. S.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Brookes, Paul S.
- ORCID
- Brookes, Paul S.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 38
- Issue
- 1
- Pages
- 12-23
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2086276885
- Cited by
- 447
- References
- 6
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 16 · 2023: 24 · 2022: 27 · 2021: 21 · 2020: 22 · 2019: 21 · 2018: 24 · 2017: 21 · 2016: 17 · 2015: 20 · 2014: 12 · 2013: 16 · 2012: 20
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial proton leak, reactive oxygen species, oxidative phosphorylation, uncoupling, reactive oxygen species generation, feedback loops, ATP production, cytoprotection, ischemic injury, mitochondrial function
- MeSH terms
- Animals, Energy Metabolism, Humans, Mitochondria, Oxidation-Reduction, Oxidative Phosphorylation, Oxygen Consumption, Protons, Uncoupling Agents, Reactive Oxygen Species, Proton Pumps, Mitochondrial Proteins
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