p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress.
Mitochondrial pathologies underlie a number of life-shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain-mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. In this study, we show that the C. elegans p53 ortholog cep-1 mediates these opposite effects. We found that cep-1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin - the protein defective in patients with Friedreich's Ataxia. Importantly, we show that cep-1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. These findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial-associated diseases.
Ventura
Natascia
N
Institute for Behavioral Genetics, University of Colorado at Boulder, 80309, USA. natascia.ventura@med.uniroma2.it
Rea
Shane L
SL
Schiavi
Alfonso
A
Torgovnick
Alessandro
A
Testi
Roberto
R
Johnson
Thomas E
TE
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004579:Electron Transport; D004734:Energy Metabolism; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000096923:Frataxin
D029742:Caenorhabditis elegans Proteins; D033862:Iron-Binding Proteins; D024101:Mitochondrial Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D000096923:Frataxin; C438244:CEP-1 protein, C elegans; C112486:EGL-1 protein, C elegans