ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast

ER-phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER-phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro-ER-phagy has been discovered, the mole...

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Hauptverfasser: Schäfer, Jasmin (VerfasserIn) , Pajonk, Oliver (VerfasserIn) , Ruffini, Giulia (VerfasserIn) , Papagiannidis, Dimitrios (VerfasserIn) , Knop, Michael (VerfasserIn) , Schuck, Sebastian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2020
In: The EMBO journal
Year: 2020, Jahrgang: 39, Heft: 2
ISSN:1460-2075
DOI:10.15252/embj.2019102586
Online-Zugang:Verlag, Volltext: https://doi.org/10.15252/embj.2019102586
Verlag: https://www.embopress.org/doi/full/10.15252/embj.2019102586
Volltext
Verfasserangaben:Jasmin A. Schäfer, Julia P. Schessner, Peter W. Bircham, Takuma Tsuji, Charlotta Funaya, Oliver Pajonk, Katharina Schaeff, Giulia Ruffini, Dimitrios Papagiannidis, Michael Knop, Toyoshi Fujimoto & Sebastian Schuck

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520 |a ER-phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER-phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro-ER-phagy has been discovered, the molecules and mechanisms mediating micro-ER-phagy remain unknown. Here, we first show that micro-ER-phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1-Spo7 phosphatase complex and the ESCRT machinery as key components for micro-ER-phagy. Third, we demonstrate that macro- and micro-ER-phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro-ER-phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis. 
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