Thursday, February 15th 2024, at 13.00 CET
Regulation of organismal proteostasis and stress resilience by reproductive and metabolic cues
Ambre Sala is a group leader at the Institute for Integrative Biology of the Cell (I2BC), in Gif-sur-Yvette. She is interested in the mechanisms that orchestrate proteostasis in different cell types and their impact on age-dependent tissue and organismal decline. Her group uses Caenorhabditis elegans to model age-dependent protein phase transitions and interrogate the role of proteostasis network components, with a focus on molecular chaperones.
Webinar Summary: Maintaining a functional proteome is critical to cell survival and is ensured by a complex network of molecular chaperones and degradation pathways that cooperate to promote proteostasis. Failure of these systems during aging is a major driver of cellular dysfunction and many age-related diseases are characterized by pathological protein misfolding and aggregation. Studies using model organisms have revealed that the age-dependent decline of proteostasis capacity is regulated by the reproductive system, with important consequences for organismal health and longevity. Using the Caenorhabditis elegans model system to interrogate the relationship between reproduction and somatic proteostasis, we uncovered a novel transcellular pathway that restores maternal proteostasis and stress resilience when the integrity of the developing embryo is compromised. We found that this pathway utilizes the remodeling of lipid metabolism via a nuclear receptor to enhance cellular resilience to proteotoxic stress. Such regulation of organismal proteostasis by integrated reproductive and metabolic cues may serve to reassess commitment to reproduction and promote somatic endurance when progeny production is not optimal.