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Periodic Report Summary 1 - CHEMBIO_ATG (Chemical biology of autophagy)

Autophagy is a cellular pathway that regulates the degradation and recycling of proteins and organelles. A normal function of this process is crucial to maintain cell survival under starving conditions, to prevent pathogen infection or to eliminate protein aggregates. However, there are growing evidences that a malfunctioning of autophagy is also related with several pathologies and associated with aging.
LC3 is the best characterized marker of autophagy. This protein exists in two forms, a soluble LC3-I and a lipidated LC3-II, bearing a phosphatidylethanolamine (PE) unit, that associates with the membrane of the autophagosome and regulates its elongation and closure.
The main goal of this project was the development of a chemical biology approach that enables the characterization of the mechanism controlling autophagy with special emphasis on the lipidation and delipidation processes regulating LC3 function and localization. With this aim, we have generated a semisynthetic lipidated LC3 protein and it has been employed to investigate the function of LC3-II in membrane tethering and fusion processes. Moreover, we are setting up a mass-based approach to characterize the lipids present in LC3-II. Future work will be directed to correlate the possible lipid diversity identified at PE-units with the membrane association properties of LC3-II.

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Life Sciences