Innovating Works

MitoCure

Financiado
Molecular and metabolic mechanisms underlying mitochondrial dysfunction
Mitochondria are essential organelles that carry out critical metabolic functions within the cells. Electron transport chain (ETC) defects occurring from mitochondrial disease mutations compromise cellular fitness and survival. Th... Mitochondria are essential organelles that carry out critical metabolic functions within the cells. Electron transport chain (ETC) defects occurring from mitochondrial disease mutations compromise cellular fitness and survival. This biochemical failure is thought to underlie pathologies associated with mitochondrial dysfunction. However, the precise metabolic processes, signaling pathways and compensatory responses resulting from a defective mitochondrial ETC that drive these fatal disorders are not entirely understood. Although diminished ATP production has been considered a hallmark of mitochondrial dysfunction, I hypothesize that other metabolic failures such as disturbed redox hemostasis due to accumulated levels of NADH can be equally detrimental. Moreover, which cell types contribute the most to the disease and whether disease-carrying cells negatively impact the function of its surrounding wild-type neighbors or distant organs remain poorly characterized. Here I propose to develop a holistic understanding of the molecular and metabolic components that contribute to cell and tissue deterioration in the context of ETC dysfunction. Our central goals are: (1) To identify novel uncharacterized genes controlling function and integrity of ETC complexes and supercomplexes (2) To define how ETC dysfunction impacts cellular metabolism with special focus on redox-sensitive pathways that might be altered as a consequence of imbalanced NAD+/NADH ratio (3) To elucidate brain-specific non cell-autonomous signaling that mediates maladaptation to mitochondrial dysfunction. In sum, MitoCure puts forward an ambitious but feasible program with the purpose of yielding novel information about genes, metabolic pathways and signaling mechanisms underlying the pathophysiology associated with mitochondrial dysfunction. ver más
31/12/2025
UAM
1M€
Duración del proyecto: 62 meses Fecha Inicio: 2020-10-23
Fecha Fin: 2025-12-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2020-10-23
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2020-STG: ERC STARTING GRANTS
Cerrada hace 5 años
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
UNIVERSIDAD AUTÓNOMA DE MADRID No se ha especificado una descripción o un objeto social para esta compañía.
Total investigadores 3183