Le Bateau Ivre de la Cellule: The origin and growth of the phagophore of autophagy
Autophagy is a conserved mechanism that is essential for cell survival in starvation and for cellular homeostasis. The autophagosome and the proteasome comprise the two main pathways for the degradation of proteins. Autophagy proceeds by the engulfment of bulk cytosol and organelles by a cup- (or boat-, hence the "Bateau" of the title) shaped double membrane sheet known as the phagophore, which matures into the autophagosome. Two protein complexes control the initiation of the phagophore: the Atg1/ULK1 kinase complex and the class III phosphatidylinositol 3-kinase (PI3KC3). ULK1 is in turn regulated downstream of the lysosomal protein kinase complex mTORC1 and its activator, the Ragulator-RagA/B-RagC/C complex. Our laboratory has been applying crystallography, electron microscopy, mass spectrometry, and allied biophysical techniques, in conjunction with cell biology approaches, to understand how these complexes are organized in three-dimensional space and time, and how their architectures underpin their regulation and activity. This has led to insights both into the shaping and scaffolding of the phagophore, and to the switching on and off of its growth.
California Institute for Quantitative Biosciences, University of California, Berkeley
Domain 4 - UMR 168 - Physical chemistry
Domain 4 - UMR 144 - Subcellular Structure and Cellular Dynamics