RT Journal Article
SR Electronic
T1 In situ structural analysis reveals membrane shape transitions during autophagosome formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.02.490291
DO 10.1101/2022.05.02.490291
A1 Anna Bieber
A1 Cristina Capitanio
A1 Philipp S. Erdmann
A1 Fabian Fiedler
A1 Florian Beck
A1 Chia-Wei Lee
A1 Delong Li
A1 Gerhard Hummer
A1 Brenda A. Schulman
A1 Wolfgang Baumeister
A1 Florian Wilfling
YR 2022
UL http://biorxiv.org/content/early/2022/05/02/2022.05.02.490291.abstract
AB Autophagosomes are unique organelles which form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves a series of membrane transformations with distinctly shaped intermediates whose ultrastructure is poorly understood. Here, we combine cell biology, correlative cryo-electron tomography (ET) and novel data analysis to reveal the step-by-step structural progression of autophagosome biogenesis at high resolution directly within yeast cells. By mapping individual structures onto a timeline based on geometric features, we uncover dynamic changes in membrane shape and curvature. Moreover, we reveal the organelle interactome of growing autophagosomes, highlighting a polar organization of contact sites between the phagophore and organelles such as the vacuole and the ER. Collectively, these findings have important implications for the contribution of different membrane sources during autophagy and for the forces shaping and driving phagophores towards closure without a templating cargo.Competing Interest StatementThe authors have declared no competing interest.