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Identification of new pathways involved in the regulation of the UPRmt reveals a crosstalk between mitochondrial stress response and insulin signaling

AutorHernando-Rodríguez, Blanca; Jarit-Cabanillas, Aitor; Kaderali, Lars; Artal-Sanz, Marta
Fecha de publicación2017
Citación21st International C. elegans Conference (2017)
ResumenDepletion of the mitochondrial prohibitin complex (PHB) shows an opposite effect on aging: it shortens lifespan in wild-type worms while it dramatically extends the longevity of the already long-lived insulin/IGF-1 signaling (IIS) mutants. Moreover, PHB depletion induces a strong mitochondrial unfolded protein response (UPRmt) in wild-type animals while this response is remarkably reduced in IIS mutants. Interestingly, some of the described UPRmt components are not required for the activation of the response upon PHB depletion. We aimed at identifying new pathways involved in the regulation of the PHB-mediated mitochondrial stress response, as well as mechanisms responsible for the opposite longevity outcomes of PHB depletion. Towards this aim, we developed a semi-automated method based on double RNAi and automated image analysis to carry out RNAi screens, in PHB-depleted wild type and IIS mutants. In addition to a big number of genes involved in protein homeostasis, we describe evolutionarily conserved developmental signal transduction pathways as essential modulators of the mitochondrial stress response. Furthermore, we report pathways regulating the UPRmt in an insulin-dependent manner. Our results suggest a difference in metabolism between PHB-depleted worms and PHB-depleted;IIS mutants and place carbohydrate and lipid metabolism as possible mechanisms contributing to the opposite effect of PHB depletion in the aging phenotype of wild type and metabolically compromised animals.
DescripciónResumen del trabajo presentado a la 21st International C. elegans Conference of the Genetics Society of America, celebrada en California, Los Angeles (US) del 21 al 25 de junio de 2017.-- et al.
URIhttp://hdl.handle.net/10261/164067
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