Project description DEENESFRITPL Mitochondrial recycling in ageing Autophagy is a cellular process that involves the degradation and recycling of cellular components. Mitochondria-selective autophagy, also known as mitophagy, focuses on the elimination of damaged or dysfunctional mitochondria and is responsible for mitochondrial quality control, preventing cellular dysfunction and disease. Mitochondria play a critical role in neurons, especially in synaptic transmission and maintenance. The key objective of the ERC-funded SynaptoMitophagy project is to investigate the role of mitochondria in age-related synaptic impairment. Researchers will use advanced technologies to monitor mitochondrial fate and mitophagy at synapses and assess the impact of mitophagy impairment on synaptic function and behaviour. Project results will provide important insight into the mitigation of age-related synaptic failure in humans. Show the project objective Hide the project objective Objective Age-dependent accumulation of damaged mitochondria and synaptic loss represent early pathological hallmarks of brain ageing leading to neuronal death. Mitochondria-selective autophagy (mitophagy) is triggered to eliminate defective organelles promoting cellular and organismal survival. Mitophagy declines with age, while its induction extends lifespan and confers neuroprotection across diverse species. Although the pivotal role of mitophagy in neuronal physiology is steadily emerging, its contribution to synaptic homeostasis remains elusive.Building on our previous pioneering studies, SynaptoMitophagy aims to reveal the molecular underpinnings of age-dependent synaptic impairment, focusing on mitochondrial maintenance and turnover. We will combine the nematode Caenorhabditis elegans, which offers a well-defined nervous system, with cutting-edge technologies, such as super resolution imaging, microfluidics and optogenetics, to manipulate spatiotemporally mitochondrial damage and monitor synaptic mitophagy at nanoscale resolution, in vivo. Mammalian neurons will be used to address the functional conservation of synaptic mitophagy components.The objectives are four-fold: 1) Establish mitophagy reporters for in vivo monitoring of mitochondrial fate at synapses during ageing and under neuroprotective conditions 2) Use optogenetic tools to stimulate synapse-restricted mitochondrial damage and, thereby, to detect mitophagy induction and its contribution to neurotransmission. 3) Characterize the synaptic defects and assess behavioral deficits arising from mitophagy impairment. 4) Conduct forward genetic screen for synaptic mitophagy modulators, towards augmenting mitochondrial quality control and resistance to age-related synaptic failure. The cumulative results of this proposal will decode the molecular mechanisms of neuronal mitophagy compartmentalization at synapses during ageing, providing critical insights with broad relevance to human health and quality of life. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidicsmedical and health sciencesbasic medicinephysiologyhomeostasis Keywords Ageing autophagy C. elegans energy metabolism mitochondria mitophagy mitochondrial proteostasis neurodegeneration neuronal imaging synapse Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2022-STG - ERC STARTING GRANTS Call for proposal ERC-2022-STG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Host institution ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON Net EU contribution € 1 500 000,00 Address 6 CHRISTOU LADA STR 10561 Athina Greece See on map Region Αττική Aττική Κεντρικός Τομέας Αθηνών Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON Greece Net EU contribution € 1 500 000,00 Address 6 CHRISTOU LADA STR 10561 Athina See on map Region Αττική Aττική Κεντρικός Τομέας Αθηνών Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00
