Objectif For many years, mitochondria were viewed as semiautonomous organelles, required only for cellular energetics. This view has been displaced by the concept that mitochondria are fully integrated into the life of the cell and that mitochondrial function and stress response rapidly affect other organelles, and even other tissues. A recent discovery from my lab demonstrated that mitochondrial metabolism regulates lysosomal degradation (Cell Metabolism, 2015), thus opening the way to investigate the mechanism behind communication between these organelles and its consequences for homeostasis. With this proposal, we want to assess how mitochondrial crosstalk with endolysosomal compartment controls cellular homeostasis and how mitochondrial dysfunction in certain tissues may account for systemic effects on the rest of the organism. EndoMitTalk will deliver significant breakthroughs on (1) the molecular mediators of endolysosomal-mitochondria communication, and how deregulation of this crosstalk alters cellular (2), and organism homeostasis (3). Our central goals are: 1a,b. To identify metabolic and physical connections mediating endolysosomal-mitochondria crosstalk; 2a. To decode the consequences of altered interorganelle communication in cellular homeostasis 2b. To study the therapeutic potential of improving lysosomal function in respiration-deficient cells; 3a. To assess how unresolved organelle dysfunction and metabolic stresses exclusively in immune cells affects organism homeostasis and lifespan. 3b. To decipher the molecular mediators by which organelle dysfunction in T cells contributes to age-associated diseases, with special focus in cardiorenal and metabolic syndromes. In sum, EndoMitTalk puts forward an ambitious and multidisciplinary but feasible program with the wide purpose of understanding and improving clinical interventions in mitochondrial diseases and age-related pathologies. Champ scientifique natural sciencesbiological sciencescell biologycell metabolismmedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Mots‑clés Mitochondria Endolysosomal system interorganelle communication T lymphocytes inflammaging cardiorenal syndrome metabolic disorder age associated-diseases Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-STG - ERC Starting Grant Appel à propositions ERC-2016-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil UNIVERSIDAD AUTONOMA DE MADRID Contribution nette de l'UE € 1 199 875,00 Adresse CALLE EINSTEIN 3 CIUDAD UNIV CANTOBLANCO RECTORADO 28049 Madrid Espagne Voir sur la carte Région Comunidad de Madrid Comunidad de Madrid Madrid Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 498 625,00 Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire UNIVERSIDAD AUTONOMA DE MADRID Espagne Contribution nette de l'UE € 1 199 875,00 Adresse CALLE EINSTEIN 3 CIUDAD UNIV CANTOBLANCO RECTORADO 28049 Madrid Voir sur la carte Région Comunidad de Madrid Comunidad de Madrid Madrid Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 498 625,00 Tiers Entité juridique autre qu’un sous-traitant qui est affiliée ou juridiquement liée à un participant. L’entité réalise des travaux dans les conditions prévues par la convention de subvention, fournit des biens ou des services pour l’action, mais n’a pas signé la convention de subvention. Le tiers respecte les règles applicables au participant qui lui est lié dans le cadre de la convention de subvention en ce qui concerne l’éligibilité des coûts et le contrôle des dépenses. FUNDACION PARA LA INVESTIGACION BIOMEDICA DEL HOSPITAL UNIVERSITARIO 12 DE OCTUBRE Espagne Contribution nette de l'UE € 298 750,00 Adresse AVENIDA DE CORDOBA SN 28041 Madrid Voir sur la carte Région Comunidad de Madrid Comunidad de Madrid Madrid Type d’activité Other Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 298 750,00