The efficiency and plasticity of mitochondrial energy transduction.
Abstract
Since it was first realized that biological energy transduction involves oxygen and ATP, opinions about the amount of ATP made per oxygen consumed have continually evolved. The coupling efficiency is crucial because it constrains mechanistic models of the electron-transport chain and ATP synthase, and underpins the physiology and ecology of how organisms prosper in a thermodynamically hostile environment. Mechanistically, we have a good model of proton pumping by complex III of the electron-transport chain and a reasonable understanding of complex IV and the ATP synthase, but remain ignorant about complex I. Energy transduction is plastic: coupling efficiency can vary. Whether this occurs physiologically by molecular slipping in the proton pumps remains controversial. However, the membrane clearly leaks protons, decreasing the energy funnelled into ATP synthesis. Up to 20% of the basal metabolic rate may be used to drive this basal leak. In addition, UCP1 (uncoupling protein 1) is used in specialized tissues to uncouple oxidative phosphorylation, causing adaptive thermogenesis. Other UCPs can also uncouple, but are tightly regulated; they may function to decrease coupling efficiency and so attenuate mitochondrial radical production. UCPs may also integrate inputs from different fuels in pancreatic beta-cells and modulate insulin secretion. They are exciting potential targets for treatment of obesity, cachexia, aging and diabetes.
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Activation of UCP2 protects the β-cell from the deleterious effects of excess ROS by dissipating the proton gradient and decreasing ROS production in a controlled negative feedback manner.
“Thus, the activation of UCP2 protects the -cell from the deleterious effects of excess ROS (257) by dissipating the proton gradient and decreasing ROS production in a controlled negative feedback manner (Fig. 4).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [257]
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- Authors
- Brand, M. D.
- Affiliations
- MRC Mitochondrial Biology Unit (GB)
- Corresponding author
- Brand, M.D.
- ORCID
- Brand, M.D.
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2005-10-26
- Volume
- 33
- Issue
- 5
- Pages
- 897-904
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W2021952329
- Cited by
- 406
- References
- 57
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 8 · 2023: 25 · 2022: 17 · 2021: 19 · 2020: 22 · 2019: 20 · 2018: 19 · 2017: 30 · 2016: 21 · 2015: 23 · 2014: 27 · 2013: 12 · 2012: 27
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitochondrial energy transduction, coupling efficiency, electron transport chain, complex I, ATP synthase, proton leak, UCP1, thermogenesis, mitochondrial uncoupling, mitochondrial reactive oxygen species, beta-cell insulin secretion, obesity, cachexia, aging, diabetes mellitus
- MeSH terms
- Adenosine Triphosphate, Animals, Energy Metabolism, Mitochondria, Models, Biological, Oxygen Consumption, Uncoupling Agents
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