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-Structure paper
Title | In situ structural analysis reveals membrane shape transitions during autophagosome formation. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 119, Issue 39, Page e2209823119, Year 2022 |
Publish date | Sep 27, 2022 |
Authors | Anna Bieber / Cristina Capitanio / Philipp S Erdmann / Fabian Fiedler / Florian Beck / Chia-Wei Lee / Delong Li / Gerhard Hummer / Brenda A Schulman / Wolfgang Baumeister / Florian Wilfling / |
PubMed Abstract | Autophagosomes are unique organelles that form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves membrane transformations of distinctly ...Autophagosomes are unique organelles that form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves membrane transformations of distinctly shaped intermediates whose ultrastructure is poorly understood. Here, we combine cell biology, correlative cryo-electron tomography (cryo-ET), and extensive data analysis to reveal the step-by-step structural progression of autophagosome biogenesis at high resolution directly within yeast cells. The analysis uncovers an unexpectedly thin intermembrane distance that is dilated at the phagophore rim. Mapping of individual autophagic structures onto a timeline based on geometric features reveals a dynamical change of membrane shape and curvature in growing phagophores. Moreover, our tomograms show the organelle interactome of growing autophagosomes, highlighting a polar organization of contact sites between the phagophore and organelles, such as the vacuole and the endoplasmic reticulum (ER). Collectively, these findings have important implications for the contribution of different membrane sources during autophagy and for the forces shaping and driving phagophores toward closure without a templating cargo. |
External links | Proc Natl Acad Sci U S A / PubMed:36122245 / PubMed Central |
Methods | EM (tomography) |
Structure data | EMDB-15526: In situ cryo-electron tomogram of a bulk autophagy phagophore in S. cerevisiae EMDB-15545: In situ cryo-electron tomogram of a bulk autophagy phagophore in S. cerevisiae #2 EMDB-15546: In situ cryo-electron tomogram of a bulk autophagy autophagosome with END cargo in S. cerevisiae #1 EMDB-15547: In situ cryo-electron tomogram of a bulk autophagy autophagosome fusing with the vacuole in S. cerevisiae #1 EMDB-15548: In situ cryo-electron tomogram of a bulk autophagy phagophore in S. cerevisiae #3 EMDB-15549: In situ cryo-electron tomogram of a bulk autophagy phagophore in S. cerevisiae #4 |
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