Project description
A new pathway for cellular secretion
Cells degrade unwanted material through a process known as autophagy: this involves membrane vesicles which encapsulate and transport degraded cargo out of the cell. The ERC-funded autoXitus project focuses on a newly discovered cellular process called autoxitus, which functions as an alternative to traditional autophagy by allowing cells to expel large cellular material such as organelles. The study aims to uncover the molecular mechanisms of autoxitus, how it is regulated, and its relationship with degradative autophagy. Researchers will also examine the role of autoxitus in stress signal transmission to neighbouring cells and in the viral life cycle.
Objective
Cells control their content by balancing its synthesis and degradation. Autophagy is a key degradation process capable of engulfing large fractions of cells, including organelles, into double-membrane vesicles called autophagosomes. These fuse with lysosomes causing degradation of their cargo. Secretory pathways, including secretory autophagy, offer an alternative option to remove unwanted materials from cells. However, mechanisms allowing the secretion of larger cellular components are still unknown.
We identified a novel pathway, which we termed autoxitus – for self (auto) exit (xitus) – that leads to the secretion of autophagosomes. This proposal aims at defining the molecular mechanism and regulation of autoxitus. We will first study how specificity and decision-making between secretory autoxitus and degradative autophagy routes is achieved and whether there is cross-regulation. Autophagosomes on the autoxitus route can contain parts of the cytosol, but also large fragments of organelles, raising the question whether the secreted autoxitus vesicles signal to neighbouring cells in a non-cell autonomous manner. We aim to uncover the impact of these signalling processes to determine whether and how autoxitus helps to signal stress conditions or may even deliver material or organelles to other cells. Finally, the role of autoxitus in two (patho-)physiological conditions will be analysed. Since autophagic processes are key to viral particle release, we will study the contribution of autoxitus to the viral life cycle. Furthermore, we will investigate the role of autoxitus in the release of protein aggregates from cells and the resulting seeding propensity.
This proposal will give ground-breaking insight into autoxitus, its molecular underpinnings and physiological consequences. AutoXitus will provide the framework for future integration into numerous cellular pathways.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
60323 Frankfurt Am Main
Germany