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
Seleccionando "Aceptar todas las cookies" acepta el uso de cookies para ayudarnos a brindarle una mejor experiencia de usuario y para analizar el uso del sitio web. Al hacer clic en "Ajustar tus preferencias" puede elegir qué cookies permitir. Solo las cookies esenciales son necesarias para el correcto funcionamiento de nuestro sitio web y no se pueden rechazar.
Cookie settings
Nuestro sitio web almacena cuatro tipos de cookies. En cualquier momento puede elegir qué cookies acepta y cuáles rechaza. Puede obtener más información sobre qué son las cookies y qué tipos de cookies almacenamos en nuestra Política de cookies.
Son necesarias por razones técnicas. Sin ellas, este sitio web podría no funcionar correctamente.
Son necesarias para una funcionalidad específica en el sitio web. Sin ellos, algunas características pueden estar deshabilitadas.
Nos permite analizar el uso del sitio web y mejorar la experiencia del visitante.
Nos permite personalizar su experiencia y enviarle contenido y ofertas relevantes, en este sitio web y en otros sitios web.