AutophagosomeSealing · Ymr1 role in the Atg proteins release from complete autophagosomes

Ymr1 role in the Atg proteins release from complete autophagosomes

Autophagy is one of the two major intracellular degradation mechanisms essential for cell survival. The basic mechanism of autophagy is the sequestration of the structures targeted to destruction by large double-membrane vesicles called autophagosomes. Autophagosomes are formed by expansion and sealing of a small membrane cistern termed the phagophore. Most efforts in studying the autophagy mechanism have been focused on the early steps of autophagosome biogenesis. While most of the proteins involved in the formation and elongation of the phagophore has been identified, the autophagy-related (Atg) proteins, it is unknown which factors are involved in autophagosome completion. This event has to be tightly regulated to coordinate the release of Atg proteins and the recruitment of fusion factors in order to avoid the premature fusion of incomplete autophagosomes with lysosomes/vacuoles (degradative compartments, in mammalian and yeast cells, respectively), which could cause an impairment of autophagy and a damage of the lysosome/vacuole. Autophagy is essential for cellular homeostasis by executing a multitude of physiological functions. Thereby, a defect in this pathway leads to severe diseases, including neurodegenerative disorders and cancer. The elucidation of the autophagy mechanism is therefore vital to understand the contribution of this pathway in the different physiological and pathological situations, and to modulate it for therapeutic purposes. The principal therapeutic targets are the genes involved in autophagy and Ymr1 is one of them. Therefore, in a long-term perspective, my results could provide knowledge essential for the development of therapies or compounds aimed to regulate autophagy. The generation of phosphatidylinositol-3-phosphate (PI3P) is fundamental for specific recruitment of Atg protein and consequently it is also one of the key factors for the autophagy initiation. In yeast, accumulated autophagosomes are sealed and Atg proteins are still present on their surface, demonstrating that PI3P turnover is required for the release of the Atg machinery once autophagosomes are completed, and this release is a prerequisite for their subsequent fusion with vacuoles The main objective of this project is to elucidate the molecular role of both Ymr1 and the PI3P turnover in autophagosome completion. Because I encountered major problems in detecting Ymr1 by live-cell imaging, I could not continue the project as initially designed. I have opted to look at PI3P relevance in autophagy following a different approach.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз