ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast

• Jasmin A Schäfer ^[2] ; Julia P Schessner ^[3] ; Peter W Bircham ^[4] ; Takuma Tsuji ^[5] ; Charlotta Funaya ^[1] ; Oliver Pajonk ^[2] ; Katharina Schaeff ^[2] ; Giulia Ruffini ^[2] ; Dimitrios Papagiannidis ^[2] ; Michael Knop ^[2] ; Toyoshi Fujimoto ^[5] ; Sebastian Schuck ^[2]
  1. [1] Heidelberg University

     Heidelberg University

     Stadtkreis Heidelberg, Alemania

     
  2. [2] 1 DKFZ‐ZMBH Alliance and CellNetworks Cluster of Excellence Center for Molecular Biology of Heidelberg University (ZMBH) Heidelberg Germany
  3. [3] 1 DKFZ‐ZMBH Alliance and CellNetworks Cluster of Excellence Center for Molecular Biology of Heidelberg University (ZMBH) Heidelberg Germany; 4Present address: Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried Germany
  4. [4] 1 DKFZ‐ZMBH Alliance and CellNetworks Cluster of Excellence Center for Molecular Biology of Heidelberg University (ZMBH) Heidelberg Germany; 5Present address: Laboratory of Systems Biology VIB Center for Microbiology/Laboratory of Genetics and Genomics CMPG KU Leuven Leuven Belgium
  5. [5] 2 Research Institute for Diseases of Old Age Juntendo University Graduate School of Medicine Tokyo Japan

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 39, Nº. 2, 2020
• Idioma: inglés
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  • 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.