Mitochondrial crosstalk signalling in the regulation of ageing. (MitoSigAge)
The project is funded by the European Research Council as a Starting Grant (StG).
Ageing is one of the most intriguing and fundamental biological processes, with clear implications for human health. Although mitochondria have been associated with ageing and age-related pathology, the underlying molecular mechanisms remain poorly understood. The most relevant genetic pathway regulating ageing is the insulin/IGF-1 signalling (IIS) pathway. Recently, we have shown that mitochondrial prohibitins (PHB) play a major role in cellular metabolism and mitochondrial biogenesis, affecting ageing in opposite ways in wild-type animals and IIS-defective C. elegans mutants.
The aim of the research programme is to shed light on the intricate interaction between mitochondria and cell-signalling networks in the regulation of ageing.
The project, hosted by UPO, aims to:
- 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 genomewide RNAi screens,
- Conduct a comprehensive metabolic profiling of wild type and IIS mutants in the presence and absence of prohibitin.
- Identify genetic suppressors of prohibitins by performing forward genetic suppressor screens. Ultimately, the functional conservation of key genes discovered in C. elegans will be investigated in mammalian assays.
Given the complexity of biological systems and disease mechanisms, high-quality genome-scale analyses will help to accelerate basic and biomedical research by facilitating the formulation of more directed hypothesis to be experimentally tested. The completion of this project will certainly gather a considerable amount of data on the complex interaction networks influencing mitochondrial function, metabolism and ageing.
The project represents an integrative and innovative approach to identify cellular signalling pathways involved in mediating lifespan-extending metabolism adjustments and their consequences. The results stemming from this research will provide fundamental insights to understand the ageing process and to combat ageing-related diseases.
Interacción de la mitocondria y las rutas de señalización celular en la regulación del envejecimiento
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Marta Artal Sanz.
Universidad Pablo de Olavide
Budget of Andalusian group: € 1,424,640.00
Universidad Pablo de Olavide (Spain)