La proteína tuberina: diana terapéutica para activar autofagia y mitofagia evitando la progresión a la diabetes tipo 2
ISSN: 1697-4298, 0034-0618
Year of publication: 2016
Volume: 82
Issue: 4
Pages: 424-442
Type: Article
More publications in: Anales de la Real Academia Nacional de Farmacia
Abstract
Cytoplasmic quality control is essential in maintaining cell viability, and particularly, β pancreatic cells, due to its huge protein synthesis capacity. In this context, it is important the activation of a physiological process called autophagy, in order to eliminate protein aggregates and damaged organelles, resulting in a reduction in the reticulum cell stress. The complex formed by hamartin and tuberin (TSC1-TSC2) has emerged as a central signal, energy status and nutrient-integrating node within the cell. This complex negatively regulates the mechanistic target of rapamycin complex 1 (mTORC1), and activates autophagy. In this proyect we aimed to further investigate new molecular mechanisms of TSC2 regulation, aswell as cytoplasmic quality control, autophagy and mitophagy ones. We propose that the TSC2 acetylation status, mediated by the deacetylation activity of sirtuin1 (SIRT1), modulates its stability and protein activity, affecting cell homeostasis.