Innovating Works

MAMllingIR

Financiado
Endoplasmic Reticulum-Mitochondria contact sites structural and functional adapt...
Endoplasmic Reticulum-Mitochondria contact sites structural and functional adaptation during Insulin Resistance The high calory intake and the sedentary behaviours represent one of the most common stress to which humanity is subjected. This is leading to an increased incidence of obesity that can be aggravated by dysfunctional metabolism, a... The high calory intake and the sedentary behaviours represent one of the most common stress to which humanity is subjected. This is leading to an increased incidence of obesity that can be aggravated by dysfunctional metabolism, among which insulin resistance (IR) is the most common scenario. Two crucial processes know to lead to IR are Endoplasmic Reticulum (ER) stress and mitochondrial dysfunction. Mitochondria and ER are in tight physical contact through the mitochondria-associated ER membranes (MAMs), which are emerging as an important hub for glucose homeostasis. MAMs are involved in a plethora of cell functions, such as lipid synthesis, ROS and Ca2+ signalling, autophagy and inflammation, all processes tightly linked with cellular insulin sensitivity. In support to this notion, MAMs miscommunication was shown to occur in the presence of IR. Nevertheless, no conclusive molecular mechanisms can explain MAMs adaptation during IR. Furthermore, how MAMs remodelling affects the signalling between ER and mitochondria (Ca2+, ROS, lipid exchange) during IR progression and how this affects ER and mitochondria functions are still open questions. The overarching aim of this proposal is to characterize the alterations of intracellular signalling in mouse models of hepatic IR at the level of MAMs and to develop a standardized methodological approach to assess inter-organelles signalling changes during pathophysiological cues. To this goal, I will implement innovative approaches in vivo to quantify these contacts and to identify the MAMs molecular composition during IR. Furthermore, I will characterize the consequence of IR on MAMs signalling pathways by combining ‘omics approaches and imaging technics, to identify the molecular and functional signature of the MAMs during the IR in vivo and characterize new molecular pathways involved in the onset of IR in the liver. ver más
30/06/2024
174K€
Perfil tecnológico estimado
Duración del proyecto: 25 meses Fecha Inicio: 2022-05-24
Fecha Fin: 2024-06-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-06-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 174K€
Líder del proyecto
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUN... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5