ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast. (5th December 2019)

• Record Type: Journal Article
• Authors: Schäfer, Jasmin A; Schessner, Julia P; Bircham, Peter W; Tsuji, Takuma; Funaya, Charlotta; Pajonk, Oliver; Schaeff, Katharina; Ruffini, Giulia; Papagiannidis, Dimitrios; Knop, Michael; Fujimoto, Toyoshi; Schuck, Sebastian
• Is Part Of: EMBO journal. Volume 39:Number 2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-12-05
• Subjects: endoplasmic reticulum -- ESCRT machinery -- microautophagy -- yeast; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2019102586
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: 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. Synopsis: Protein misfolding in yeast triggers degradation of the endoplasmic reticulum (ER) by both macro‐ and microautophagy. Micro‐ER‐phagy requires the Nem1‐Spo7 phosphatase complex and ESCRT proteins for membrane scission during uptake of multilamellar ER whorls into the lysosome. Micro‐ER‐phagy operates in parallel with macro‐ER‐phagy but does not require the machinery for autophagosome formation. Micro‐ER‐phagy involves the generation of multilamellar ER whorls, which arise from stacks of cisternal ER. The Nem1‐Spo7 phosphatase complex and ESCRT proteins are essential for micro‐ER‐phagy. The ESCRT machinery promotes lysosome membrane scission as the final step of microautophagy of ER whorls. Abstract : Micro‐ER‐phagy requires the Nem1‐Spo7 phosphatase complex and ESCRT proteins for membrane scission during uptake of multilamellar ER whorls into the lysosome.