A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress

Madlen Stephani, Lorenzo Picchianti, Alexander Gajic, Rebecca Beveridge, Emilio Skarwan, Victor Sanchez de Medina Hernandez, Azadeh Mohseni, Marion Clavel, Yonglung Zeng, Christin Naumann, Mateusz Matuszkiewicz, Eleonora Turco, Christian Loefke, Baiying Li, Gerhard Durnberger, Michael Schutzbier, Hsiao Tieh Chen, Alibek Abdrakhmanov, Adriana Savova, Khong-Sam ChiaArmin Djamei, Irene Schaffner, Steffen Abel, Liwen Jiang, Karl Mechtler, Fumiyo Ikeda, Sascha Martens, Tim Clausen, Yasin Dagdas

Research output: Working paper

Abstract

Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control at the ER.
Original languageEnglish
Place of PublicationCold Spring Harbor, NY.
Number of pages83
DOIs
Publication statusPublished - 24 Mar 2020

Keywords

  • endoplasmic reticulum
  • heterogeneous cellular network
  • autophagy

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    Stephani, M., Picchianti, L., Gajic, A., Beveridge, R., Skarwan, E., Sanchez de Medina Hernandez, V., ... Dagdas, Y. (2020). A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress. Cold Spring Harbor, NY. https://doi.org/10.1101/2020.03.18.995316