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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Veröffentlicht in:	Nature (London) Jg. 578; H. 7794; S. 301 - 305
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 13.02.2020 Nature Publishing Group
Schlagworte:	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
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-020-1977-6