Cited by 112Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsCell death mechanisms and regulation

Lifespan and mitochondrial control of neurodegeneration

Wright, Alan F, Jacobson, Samuel G, Cideciyan, Artur V, Roman, Alejandro J, Shu, Xinhua, Vlachantoni, Dafni, McInnes, Roderick R, Riemersma, Rudolph A·2004·Nature Genetics

Abstract

We examine the allometric (comparative scaling) relationships between rates of neurodegeneration resulting from equivalent mutations in a diverse group of genes from five mammalian species with different maximum lifespan potentials. In both retina and brain, rates of neurodegeneration vary by as much as two orders of magnitude and are strongly correlated with maximum lifespan potential and rates of formation of mitochondrial reactive oxygen and nitrogen species (RONS). Cell death in these disorders is directly or indirectly regulated by the intrinsic mitochondrial cell death pathway. Mitochondria are the main source of RONS production and integrate cellular stress signals to coordinate the intrinsic pathway. We propose that these two functions are intimately related and that steady-state RONS-mediated signaling or damage to the mitochondrial stress-integration machinery is the principal factor setting the probability of cell death in response to a diverse range of cellular stressors. This provides a new and unifying framework for investigating neurodegenerative disorders.

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Crossref · 10.1038/ng1448

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Authors
Wright, A. F., Jacobson, S. G., Cideciyan, A. V., Roman, A. J., Shu, X., Vlachantoni, D., McInnes, R. R., & Riemersma, R. A.
Affiliations
  • Western General Hospital (GB)
  • University of Pennsylvania (US)
  • University of Toronto (CA)
  • UiT The Arctic University of Norway (NO)
Corresponding author
Wright, Alan F
Venue
Nature Genetics
Published
2004-10-28
Volume
36
Issue
11
Pages
1153-1158
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2050863429
Cited by
111
References
53
Citations by year
2026: 4 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 3
FWCI
0.46
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • ResearchOnline (Glasgow Caledonian University) (acceptedVersion)
Funders
  • Macula Vision Research Foundation
  • 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 › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
neurodegeneration, lifespan, allometric scaling, retina, brain, mammalian species comparison, genetic mutations
MeSH terms
Animals, Brain, Humans, Life Expectancy, Mitochondria, Nerve Degeneration, Retina, Species Specificity, Cell Death, Reactive Oxygen Species, Oxidative Stress, Neurodegenerative Diseases, Reactive Nitrogen Species

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