Abstract 1064 A mitochondrial unfolded protein response (mitoUPR)-independent role of DVE-1 in longevity regulation

cAMP, protein kinase A, membrane contact sites, phosphodisterases AMP and its effector PKA are key regulators of cellular function.cAMP signalling is organized into a complex network of distinct, yet interconnected pathways, driven by sharp subcellular cAMP gradients that are restricted within nanodomains.Defective cAMP/PKA signalling is a hallmark of multiple disease conditions.This signalling pathway is targeted by a large number of current medication, which however often remain unsatisfactory and need improvement.Current therapeutic strategies largely ignore signalling processes occurring in cardiomyocytes at the subcellular level.Phosphodiesterases (PDEs), which hydrolyse cAMP, play a critical role in shaping intracellular cAMP gradients.Our recent research, utilizing real-time imaging and targeted FRET reporters in conjunction with proteomics approaches, has uncovered multiple cAMP nanodomains and their associated PDEs at membrane contact sites.This reveals an unrecognized function of cAMP as a regulator of signalling within these specialized subcellular locations.Dissecting cAMP signalling at membrane contact sites may provide novel mechanistic understanding of pathological processes and may guide development of new strategies for targeted therapeutic interventions.