Alteration of Mfn2 protein and Endoplasmic Reticulum to Mitochondria calciUm transfer in STress

ended

Stress conditions threaten the organism’s homeostasis triggering adaptative responses. One of them is the increased energy demand from the brain. When stress becomes chronic, it leads to behavioural changes that range from adaptation to psychopathology. aMUST project aims to understand the neurobiological mechanisms underlying stress response. Considering that nowadays chronic stress is a risk factor for psychopathologies, such as anxiety and depression, with 25% of incidence in the population and an economical burden of €170 billion/year in EU, the aMUST project is extremely relevant and timely. Mitochondria and bioenergetics are emerging as important key players in stress-related pathologies. Whereas the energy-related impact of stress has received considerable attention in the past few years, the critical importance of the specialized cellular hubs called mitochondrial-endoplasmic reticulum (ER) associated membranes (MAMs) in stress responses, remains to be elucidated. Combining cutting-edge approaches, the aMUST project will shed light on this crucial biological question. Accordingly, intracranial lenses insertion of the mini endoscope in stress-vulnerable brain regions will be used to allow the study of in vivo mitochondrial calcium dynamics during behavioral experiments. 3D electron microscopy, protein ligase assay and BioID in vivo proteomics will allow to determine composition in MAMs structures and which protein interactions are altered during stress. The use of transgenic animals, compounds that change MAMs proteins function and alleviate ER-stress will be used to prevent possible modifications that cause vulnerability to stress. Therefore, aMUST project outcomes will unveil the MAMs-related mechanisms needed to open new therapeutic avenues to promote resilience to stress.