Nature (London), 2020-02, Vol.578 (7794), p.301-305
2020
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- Autor(en) / Beteiligte
- Titel
- Phase separation organizes the site of autophagosome formation
- Ist Teil von
- Nature (London), 2020-02, Vol.578 (7794), p.301-305
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Many biomolecules undergo liquid-liquid phase separation to form liquid-like condensates that mediate diverse cellular functions . 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 . 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-020-1977-6Titel-ID: cdi_proquest_miscellaneous_2352052934
- Format
- –
- Schlagworte
- 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, Kinases, Liquid phases, Localization, Mechanistic Target of Rapamycin Complex 1 - chemistry, Mechanistic Target of Rapamycin Complex 1 - metabolism, Membrane structures, Membranes, Microscopy, 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, Vacuoles - metabolism, Yeast fungi