Uncoupling proteins: A role in protection against reactive oxygen species—or not?
Open accessAbstract
A physiological function of the original uncoupling protein, UCP1, is well established: UCP1 is the molecular background for nonshivering thermogenesis. The functions of the "novel" UCPs, UCP2 and UCP3, are still not established. Recent discussions imply that all UCPs may play a role in protection against reactive oxygen species (ROS). Here we examine critically the evidence that UCP1, UCP2 and UCP3 are stimulated by ROS (superoxide) or ROS products (4-hydroxy-2-nonenal), and that the UCPs actually diminish oxidative damage. We conclude that, concerning UCP1, it is unlikely that it has such a role; concerning UCP2/UCP3, most evidence for physiologically significant roles in this respect is still circumstantial.
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Although nonmitochondrial sources of ROS exist during ischemia, the majority of ROS are likely derived from the mitochondrial respiratory complexes.
“Although nonmitochondrial sources of ROS exist during ischemia [e.g., NAD(P)H oxidase (141, 188, 328) and xanthine oxidase (25) in vasculature], the majority of ROS are likely derived from the mitochondrial respiratory complexes, as shown by the damage to respiratory complexes (212, 213, 245) and the effect of mitochondrial inhibitors (5, 28, 71, 81–86).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [71]
Isolated hearts exhibit a hypothermia-dependent linear increase in both O2•− and ONOO−.
“Isolated hearts exhibit a hypothermia-dependent linear increase in both O2•− (Figs. 6 and 15) and ONOO− (Fig. 7) (71).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [71]
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References 75 · Cited by 182
- Authors
- Cannon, B., Shabalina, I. G., Kramarova, T. V., Petrovic, N., & Nedergaard, J.
- Affiliations
- Stockholm University (SE)
- Corresponding author
- Cannon, Barbara
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 1757
- Issue
- 5-6
- Pages
- 449-458
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2039686675
- Cited by
- 182
- References
- 75
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 13 · 2017: 1 · 2016: 6 · 2015: 11 · 2014: 15 · 2013: 7 · 2012: 15
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- 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
- uncoupling proteins, UCP1, UCP2, UCP3, reactive oxygen species, superoxide, 4-hydroxynonenal, oxidative damage, non-shivering thermogenesis, antioxidant function
- MeSH terms
- Uncoupling Protein 2, Uncoupling Protein 3, Uncoupling Protein 1, Aldehydes, Animals, Carrier Proteins, Humans, Ion Channels, Membrane Proteins, Purine Nucleotides, Superoxides, Reactive Oxygen Species, Oxidative Stress, Mitochondrial Proteins, Membrane Transport Proteins
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