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ESCRT-III-driven piecemeal micro-ER-phagy remodels the ER during recovery from ER stress

  • Loi, Marisa Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Biology, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland
  • Raimondi, Andrea Experimental Imaging Center, San Raffaele Scientific Institute, 20132 Milan, Italy
  • Morone, Diego Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Molinari, Maurizio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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    07.11.2019
Published in:
  • Nature communications. - 2019, vol. 10, p. 5058
Autophagy
Endoplasmic reticulum
Stress signalling
English The endoplasmic reticulum (ER) produces about 40% of the nucleated cell’s proteome. ER size and content in molecular chaperones increase upon physiologic and pathologic stresses on activation of unfolded protein responses (UPR). On stress resolution, the mammalian ER is remodeled to pre-stress, physiologic size and function on activation of the LC3-binding activity of the translocon component SEC62. This elicits recov-ER- phagy, i.e., the delivery of the excess ER generated during the phase of stress to endolysosomes (EL) for clearance. Here, ultrastructural and genetic analyses reveal that recov-ER-phagy entails the LC3 lipidation machinery and proceeds via piecemeal micro- ER-phagy, where RAB7/LAMP1-positive EL directly engulf excess ER in processes that rely on the Endosomal Sorting Complex Required for Transport (ESCRT)-III component CHMP4B and the accessory AAA+ ATPase VPS4A. Thus, ESCRT-III-driven micro-ER- phagy emerges as a key catabolic pathway activated to remodel the mammalian ER on recovery from ER stress.
Language
  • English
Classification
Biological sciences
License
CC BY
Open access status
gold
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https://n2t.net/ark:/12658/srd1319161
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