A shape to fit the need: how cell rearrange their organelle composition and architecture during development and stress (PRIN 2017, codice 2017XA5J5N)

Our proposal investigates how cells reshape their organelles during development towards a secretory specialization, focusing on the mitochondria-endoplasmic reticulum (ER) contacts. It starts from the assumption that a higher ATP demand imposed by increased ER protein folding and degradation could be satisfied by formation of functional contacts with mitochondria. Revisiting mitochondrial-associated membranes (MAM) biogenesis under dynamic conditions will allow identifying molecules and patterns induced to satisfy the increased energetic demand. To this end, we will deploy state of the art quantitative proteomics and imaging technologies to analyze cellular systems induced to synthesize abundant secretory proteins with different fates, recently developed and characterized in our labs (Bakunts et al., 2017). Do MAM increase/change in parallel to the expansion of the secretory pathway? Does an increased ATP demand in the ER induce more/tighter MAM? Do different cargoes impact the outcome, and if so how? Does the unfolded protein response drive MAM reshaping, and if so via which branch(es)? Our experiments will shed light on fundamental functions of eukaryotic cells with relevance for various diseases that originate from altered ER and mitochondrial functions.