Lifespan and mitochondrial control of neurodegeneration

Alan F. Wright, Samuel G Jacobson, Artur V Cideciyan, Alejandro J Roman, Xinhua Shu, Dafni Vlachantoni, Roderick R. McInnes, Rudolf A. Riemersma

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)1153-1158
JournalNature Genetics
Volume36
Issue number11
DOIs
Publication statusPublished - 28 Oct 2004

Fingerprint

Reactive Nitrogen Species
Reactive Oxygen Species
Cell Death
Neurodegenerative Diseases
Retina
Mitochondria
Mutation
Brain
Genes

Keywords

  • mitochondrial control
  • Neurodegeneration
  • lifespan

Cite this

Wright, A. F., Jacobson, S. G., Cideciyan, A. V., Roman, A. J., Shu, X., Vlachantoni, D., ... Riemersma, R. A. (2004). Lifespan and mitochondrial control of neurodegeneration. Nature Genetics, 36(11), 1153-1158. https://doi.org/10.1038/ng1448
Wright, Alan F. ; Jacobson, Samuel G ; Cideciyan, Artur V ; Roman, Alejandro J ; Shu, Xinhua ; Vlachantoni, Dafni ; McInnes, Roderick R. ; Riemersma, Rudolf A. / Lifespan and mitochondrial control of neurodegeneration. In: Nature Genetics. 2004 ; Vol. 36, No. 11. pp. 1153-1158.
@article{86cf126b7cd34826a881a467b013c475,
title = "Lifespan and mitochondrial control of neurodegeneration",
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.",
keywords = "mitochondrial control, Neurodegeneration, lifespan",
author = "Wright, {Alan F.} and Jacobson, {Samuel G} and Cideciyan, {Artur V} and Roman, {Alejandro J} and Xinhua Shu and Dafni Vlachantoni and McInnes, {Roderick R.} and Riemersma, {Rudolf A.}",
year = "2004",
month = "10",
day = "28",
doi = "10.1038/ng1448",
language = "English",
volume = "36",
pages = "1153--1158",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Springer Nature",
number = "11",

}

Wright, AF, Jacobson, SG, Cideciyan, AV, Roman, AJ, Shu, X, Vlachantoni, D, McInnes, RR & Riemersma, RA 2004, 'Lifespan and mitochondrial control of neurodegeneration', Nature Genetics, vol. 36, no. 11, pp. 1153-1158. https://doi.org/10.1038/ng1448

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, Rudolf A.

In: Nature Genetics, Vol. 36, No. 11, 28.10.2004, p. 1153-1158.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lifespan and mitochondrial control of neurodegeneration

AU - Wright, Alan F.

AU - Jacobson, Samuel G

AU - Cideciyan, Artur V

AU - Roman, Alejandro J

AU - Shu, Xinhua

AU - Vlachantoni, Dafni

AU - McInnes, Roderick R.

AU - Riemersma, Rudolf A.

PY - 2004/10/28

Y1 - 2004/10/28

N2 - 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.

AB - 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.

KW - mitochondrial control

KW - Neurodegeneration

KW - lifespan

U2 - 10.1038/ng1448

DO - 10.1038/ng1448

M3 - Article

VL - 36

SP - 1153

EP - 1158

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 11

ER -

Wright AF, Jacobson SG, Cideciyan AV, Roman AJ, Shu X, Vlachantoni D et al. Lifespan and mitochondrial control of neurodegeneration. Nature Genetics. 2004 Oct 28;36(11):1153-1158. https://doi.org/10.1038/ng1448