IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans

IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans

Author Ferraz, Rafael C. Autor UNIFESP Google Scholar
Camara, Henrique Autor UNIFESP Google Scholar
Souza, Evandro Araujo de Autor UNIFESP Google Scholar
Pinto, Silas Autor UNIFESP Google Scholar
Pinca, Ana Paula Forti Autor UNIFESP Google Scholar
Silva, Richard Cardoso da Autor UNIFESP Google Scholar
Sato, Vitor Neves Autor UNIFESP Google Scholar
Castilho, Beatriz Amaral de Autor UNIFESP Google Scholar
Mori, Marcelo Alves da Silva Autor UNIFESP Google Scholar
Abstract Background: The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. Results: Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. Conclusions: IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR.
Keywords IMPACT
GCN2
Dietary restriction
Integrated stress response
Aging
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor National Institutes of Health (NIH) Office of Research Infrastructure Programs
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number NIH Office of Research Infrastructure Programs: P40 OD010440
CNPq: 444424/2014-8
CNPq: 474397/2011-4
FAPESP: 2010/52557-0
FAPESP: 2015/01316-7
FAPESP: 2015/04264-8
FAPESP: 2012/24490-4
FAPESP: 2009/52047-5
FAPESP: 2014/17145-4
FAPESP: 2012/04064-0
FAPESP: 2014/25068-0
FAPESP: 2014/25270-3
FAPESP: 2014/10814-8
Date 2016
Published in Bmc Biology. London, v. 14, p. -, 2016.
ISSN 1741-7007 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Origin http://dx.doi.org/10.1186/s12915-016-0301-2
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000384947100001
URI https://repositorio.unifesp.br/handle/11600/56908

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