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Mitochondrial uncoupling and lifespan
Open accessAbstract
The quest to understand why we age has given rise to numerous lines of investigation that have gradually converged to include metabolic control by mitochondrial activity as a major player. That is, the ideal balance between nutrient uptake, its transduction into usable energy, and the mitigation of damaging byproducts can be regulated by mitochondrial respiration and output (ATP, reactive oxygen species (ROS), and heat). Mitochondrial inefficiency through proton leak, which uncouples substrate oxidation from ADP phosphorylation, can comprise as much as 30% of the basal metabolic rate. This uncoupling is hypothesized to protect cells from conditions that favor ROS production. Uncoupling can also occur through pharmacological induction of proton leak and activity of the uncoupling proteins. Mitochondrial uncoupling is implicated in lifespan extension through its effects on metabolic rate and ROS production. However, evidence to date does not suggest a consistent role for uncoupling in lifespan. The purpose of this review is to discuss recent work examining how mitochondrial uncoupling impacts lifespan.
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“Mitochondria are essential regulators of cellular bioenergetics that respond to changes in environmental stimuli, such as hormones, nutrients, and oxygen tension (47, 94, 99, 109, 290, 301, 385).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [301]
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Metadata
- Authors
- Mookerjee, S. A., Divakaruni, A. S., Jastroch, M., & Brand, M. D.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Mookerjee, Shona A.
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 131
- Issue
- 7-8
- Pages
- 463-472
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC2924931
- OpenAlex
- W2061352989
- Cited by
- 169
- References
- 149
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 4 · 2023: 8 · 2022: 13 · 2021: 17 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 7 · 2016: 7 · 2015: 12 · 2014: 13 · 2013: 6 · 2012: 10
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- Funders
- National Institute on Aging (R01AG033542, PL1AG032118, P01AG025901, P30AG025708)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial uncoupling, lifespan extension, aging, proton leak, uncoupling proteins, reactive oxygen species, mitochondrial respiration, basal metabolic rate, substrate oxidation, ADP phosphorylation, thermogenesis
- MeSH terms
- Adenosine Triphosphate, Age Factors, Aging, Animals, Energy Metabolism, Glucose, Humans, Insulin, Longevity, Mitochondria, Reactive Oxygen Species, Oxidative Stress, Mitochondrial Proteins, Caloric Restriction
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