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The dynamin-related protein DRP-1 and the insulin signaling pathway cooperate to modulate Caenorhabditis elegans longevity.
Aging Cell. 2011 Aug; 10(4):724-8
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22 Jul 2011
Nektarios Tavernarakis
F1000 Cell Biology
Foundation for Research and Technology-Hellas,
Heraklion, Crete, Greece.
F1000 Cell Biology
Foundation for Research and Technology-Hellas,
Heraklion, Crete, Greece.
Maria Markaki
F1000 Cell Biology
Foundation for Research and Technology-Hellas,
Heraklion, Crete, Greece.
F1000 Cell Biology
Foundation for Research and Technology-Hellas,
Heraklion, Crete, Greece.
DOI: 10.3410/f.12062957.13206055
This paper demonstrates for the first time that mitochondrial fission and fusion processes (collectively termed mitochondrial dynamics) can influence longevity in animals. In Caenorhabditis elegans, inactivation of drp-1, which encodes the dynamin-related protein DRP-1, synergizes with the insulin/I1...Continue reading
This paper demonstrates for the first time that mitochondrial fission and fusion processes (collectively termed mitochondrial dynamics) can influence longevity in animals. In Caenorhabditis elegans, inactivation of drp-1, which encodes the dynamin-related protein DRP-1, synergizes with the insulin/IGF-1 pathway to further increase the lifespan of mutants with reduced insulin/IGF-1 signaling.
Mitochondrial fission and fusion processes are important for many cellular functions including energy metabolism, development, ageing and cell death {1}. The core molecular machineries mediating mitochondrial dynamics are evolutionarily conserved. In C. elegans, DRP-1 is involved in mitochondrial outer membrane division. The authors provide compelling evidence that inactivation of drp-1 specifically synergizes with mutations decreasing the activity of the insulin/IGF-1 pathway, such as the hormone receptor daf-2 mutation and the phosphatidylinositol 3-kinase age-1 mutation, to substantially extend lifespan. This process occurs in a daf-16-dependent manner. Surprisingly, drp-1 inactivation renders both wild-type and insulin/IGF-1 mutants vulnerable to stress. Potential mechanisms that could underlie the beneficial effect of drp-1 inactivation on longevity of insulin/IGF-1 pathway mutants are discussed.
Mitochondrial fission and fusion processes are important for many cellular functions including energy metabolism, development, ageing and cell death {1}. The core molecular machineries mediating mitochondrial dynamics are evolutionarily conserved. In C. elegans, DRP-1 is involved in mitochondrial outer membrane division. The authors provide compelling evidence that inactivation of drp-1 specifically synergizes with mutations decreasing the activity of the insulin/IGF-1 pathway, such as the hormone receptor daf-2 mutation and the phosphatidylinositol 3-kinase age-1 mutation, to substantially extend lifespan. This process occurs in a daf-16-dependent manner. Surprisingly, drp-1 inactivation renders both wild-type and insulin/IGF-1 mutants vulnerable to stress. Potential mechanisms that could underlie the beneficial effect of drp-1 inactivation on longevity of insulin/IGF-1 pathway mutants are discussed.
References
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Mitochondrial dynamics in model organisms: what yeasts, worms and flies have taught us about fusion and fission of mitochondria.
Semin Cell Dev Biol 2010 Aug; 6(21):542-9
PMID: 20006727
Disclosures
None declared
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Tavernarakis N and Markaki M: F1000Prime Recommendation of [Yang CC et al., Aging Cell 2011, 10(4):724-8]. In F1000Prime, 22 Jul 2011; DOI: 10.3410/f.12062957.13206055. F1000Prime.com/12062957#eval13206055
F1000Prime Recommendations, Dissents and Comments for [Yang CC et al., Aging Cell 2011, 10(4):724-8]. In F1000Prime, 22 May 2013; F1000Prime.com/12062957
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Here, we report that inactivation of the Caenorhabditis elegans dynamin-related protein DRP-1, a key component responsible for mitochondrial fission and conserved from yeast to humans, dramatically enhanced the effect of reduced insulin signaling (IIS) to extend lifespan. This represents the first report of a beneficial impact of manipulating mitochondrial dynamics on animal lifespan and suggests that mitochondrial morphology and IIS cooperate to modulate aging.
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
DOI: 10.1111/j.1474-9726.2011.00711.x
PMID: 21463460
