Decision making in autophagy How to loose specificity
Autophagy is a pivotal recycling pathway that operates in all eukaryotic cells. More than 40 AuTophaGy related (Atg) proteins are known in yeast and many of them are conserved in humans. In non-stressed, vegetative cells, autophagy mainly recycles unwanted or damaged cytoplasmic components by exclusively engulfing them into autophagic membrane sacks, termed phagophores. In stressed cells, however, autophagy looses its selectivity and degrades bulk cytoplasm. The regulation of this dramatic loss in selectivity is intimately intertwined with the onset of human diseases such as neurodegeneration or cancer. Its molecular bases remained, however, not well understood. Through a combination of classical biochemistry and cell biology with cutting edge in vitro reconstitutions, we have able to solve the long standing question how selectivity is regulated at a molecular level in yeast. We found that the decision is made at the earliest step in autophagy, i.e. nucleation of the phagophore.
Institut Pasteur, Department of Cell Biology and Infection
Domain 4 - UMR 144 - Subcellular Structure and Cellular Dynamics