RRC ID 6314
Author Artal-Sanz M, Tavernarakis N.
Title Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans.
Journal Nature
Abstract Marked alterations in cellular energy metabolism are a universal hallmark of the ageing process. The biogenesis and function of mitochondria, the energy-generating organelles in eukaryotic cells, are primary longevity determinants. Genetic or pharmacological manipulations of mitochondrial activity profoundly affect the lifespan of diverse organisms. However, the molecular mechanisms regulating mitochondrial biogenesis and energy metabolism during ageing are poorly understood. Prohibitins are ubiquitous, evolutionarily conserved proteins, which form a ring-like, high-molecular-mass complex at the inner membrane of mitochondria. Here, we show that the mitochondrial prohibitin complex promotes longevity by modulating mitochondrial function and fat metabolism in the nematode Caenorhabditis elegans. We found that prohibitin deficiency shortens the lifespan of otherwise wild-type animals. Notably, knockdown of prohibitin promotes longevity in diapause mutants or under conditions of dietary restriction. In addition, prohibitin deficiency extends the lifespan of animals with compromised mitochondrial function or fat metabolism. Depletion of prohibitin influences ATP levels, animal fat content and mitochondrial proliferation in a genetic-background- and age-specific manner. Together, these findings reveal a novel mechanism regulating mitochondrial biogenesis and function, with opposing effects on energy metabolism, fat utilization and ageing in C. elegans. Prohibitin may have a similar key role in modulating energy metabolism during ageing in mammals.
Volume 461(7265)
Pages 793-7
Published 2009-10-8
DOI 10.1038/nature08466
PII nature08466
PMID 19812672
MeSH Adenosine Triphosphate / metabolism Aging / physiology* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology Caloric Restriction Energy Metabolism / genetics Energy Metabolism / physiology Gene Knockdown Techniques Intestines / metabolism Lipid Metabolism / genetics Lipid Metabolism / physiology Longevity / genetics Longevity / physiology Mitochondria / metabolism* Mitochondria / physiology Mutation / genetics Repressor Proteins / genetics Repressor Proteins / metabolism* Signal Transduction*
IF 41.577
Times Cited 92
C.elegans tm0326 tm2571