Mitochondrial crosstalk signalling in the regulation of ageing

Objetivo

Mitochondrial defects are associated with aging and age-related pathology, but the molecular mechanisms regulating mitochondrial function during ageing are poorly understood. The most relevant genetic pathway regulating ageing is the insulin/IGF-1 signalling (IIS) pathway. The mitochondrial prohibitin (PHB) complex influences cellular metabolism and mitochondrial biogenesis, affecting ageing in opposite ways in wild-type animals and IIS-defective C. elegans mutants. The aim of the proposed research programme is to shed light on the intricate communication between mitochondria and cell-signalling networks in the regulation of ageing. Our specific objectives are: 1-Elucidate the cellular signalling pathways involved in the metabolic responses to mitochondrial dysfunction upon PHB depletion in wild type animals and IIS-defective mutants, using genome-wide RNAi screens, 2-Conduct a comprehensive metabolic profiling of wild type and IIS mutants in the presence and absence of prohibitins and 3-Identify genetic suppressors of prohibitins by performing forward genetic suppressor screens. As an ultimate goal, genes discovered in C. elegans will be tested in vertebrate assays for a conserved role in ageing. We will implement an interdisciplinary approach that combines the genetic power of C. elegans with state-of-the-art metabolomic approaches as well as automated sorting and optical imaging technologies to monitor fat content and mitochondrial biogenesis, in a genome-wide scale, in vivo. The fine-tuning of cellular metabolism, by integration of diverse signalling inputs is the molecular basis of longevity. This project represents a truly integrative and innovative approach to identify cellular signalling pathways involved in mediating lifespan-extending metabolism adjustments, and what these metabolic adjustments entail. These studies will provide fundamental insights to understand the ageing process and to combat ageing-related diseases.

Ámbito científico

Régimen de financiación

ERC-SG - ERC Starting Grant

Institución de acogida

UNIVERSIDAD PABLO DE OLAVIDE

Aportación de la UE

€ 1 424 640,00

Dirección

CARRETERA DE UTRERA KM 1
41013 Sevilla
España

Región

Sur Andalucía Sevilla

Tipo de actividad

Higher or Secondary Education Establishments

Contacto administrativo

Marta Mercado (Ms.)

Investigador principal

Marta Artal Sanz (Dr.)

Enlaces

Contactar con la organización Sitio web

Coste total

Sin datos

Beneficiarios (1)