Phase separation organizes the site of autophagosome formation

Many biomolecules undergo liquid–liquid phase separation to form liquid-like condensates that mediate diverse cellular functions 1 , 2 . Autophagy is able to degrade such condensates using autophagosomes—double-membrane structures that are synthesized de novo at the pre-autophagosomal structure (PAS...

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Bibliographic Details
Published in:Nature (London) Vol. 578; no. 7794; pp. 301 - 305
Main Authors: Fujioka, Yuko, Alam, Jahangir Md, Noshiro, Daisuke, Mouri, Kazunari, Ando, Toshio, Okada, Yasushi, May, Alexander I., Knorr, Roland L., Suzuki, Kuninori, Ohsumi, Yoshinori, Noda, Nobuo N.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 13.02.2020
Nature Publishing Group
Subjects:
13/1
14/19
14/33
14/35
631/57/2267
631/80/39
631/80/458
82/83
Adaptor Proteins, Signal Transducing - chemistry
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Autophagosomes - chemistry
Autophagosomes - metabolism
Autophagy
Autophagy (Cytology)
Autophagy-Related Proteins - chemistry
Autophagy-Related Proteins - genetics
Autophagy-Related Proteins - metabolism
Biomolecules
Condensates
Droplets
Experiments
Fragility
Humanities and Social Sciences
Kinases
Liquid phases
Localization
Mechanistic Target of Rapamycin Complex 1 - chemistry
Mechanistic Target of Rapamycin Complex 1 - metabolism
Membrane structures
Membranes
Microscopy
multidisciplinary
Multiprotein Complexes - chemistry
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Mutation
Observations
Phagocytosis
Phagosomes
Phase separation
Phase transformations (Statistical physics)
Phosphorylation
Physiological aspects
Point Mutation
Protein Binding
Protein interaction
Protein Kinases - chemistry
Protein Kinases - genetics
Protein Kinases - metabolism
Proteins
Saccharomyces cerevisiae - chemistry
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Science
Science (multidisciplinary)
Vacuoles - metabolism
Yeast fungi
Japan
ISSN:0028-0836, 1476-4687, 1476-4687
Online Access:Get full text
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Summary:Many biomolecules undergo liquid–liquid phase separation to form liquid-like condensates that mediate diverse cellular functions 1 , 2 . Autophagy is able to degrade such condensates using autophagosomes—double-membrane structures that are synthesized de novo at the pre-autophagosomal structure (PAS) in yeast 3 – 5 . Whereas Atg proteins that associate with the PAS have been characterized, the physicochemical and functional properties of the PAS remain unclear owing to its small size and fragility. Here we show that the PAS is in fact a liquid-like condensate of Atg proteins. The autophagy-initiating Atg1 complex undergoes phase separation to form liquid droplets in vitro, and point mutations or phosphorylation that inhibit phase separation impair PAS formation in vivo. In vitro experiments show that Atg1-complex droplets can be tethered to membranes via specific protein–protein interactions, explaining the vacuolar membrane localization of the PAS in vivo. We propose that phase separation has a critical, active role in autophagy, whereby it organizes the autophagy machinery at the PAS. The pre-autophagosomal structure in yeast is a liquid-like condensate of Atg proteins whose phase separation may have a critical, active role in autophagy.
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ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-020-1977-6