A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
- Gregor Mendel Institute, Vienna Biocenter, Austria
- Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Austria
- The Chinese University of Hong Kong, Hong Kong
- Leibniz Institute of Plant Biochemistry, Germany
- University of Vienna, Austria
- Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Austria
- IPK Gatersleben, Germany
- University of Natural Resources and Life Sciences, Austria
- the Chinese University of Hong Kong, Hong Kong
- Research Institute of Molecular Pathology, Austria
- Medical Institute of Bioregulation (MIB), Kyushu University, Japan
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 in the ER.
Data availability
All the raw data associated with the figures are uploaded to Dryad and accessible here doi:10.5061/dryad.wm37pvmkb. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD019988.
Article and author information
Author details
Funding
Vienna Science and Technology Fund (LS17-047)
- Madlen Stephani
- Lorenzo Picchianti
- Tim Clausen
- Yasin Dagdas
Austrian Science Fund (P32355)
- Yasin Dagdas
Austrian Science Fund (P30401-B21)
- Sascha Martens
Austrian Science Fund (I3033-B22)
- Armin Djamei
Austrian Science Fund (Unidocs fellowship)
- Adriana Savova
Austrian Academy of Sciences
- Alexander Gajic
- Emilio Skarwan
- Victor Sanchez de Medina Hernandez
- Azadeh Mohseni
- Marion Clavel
- Christian Loefke
- Alibek Abdrakhmanov
- Yasin Dagdas
Horizon 2020 Framework Programme (No.646653)
- Sascha Martens
The Financial Supports for Young Scientists International Research Scholarship Fund (BWM 315/2018)
- Mateusz Matuszkiewicz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Stephani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 9,297
- views
-
- 1,569
- downloads
-
- 166
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
eLife 9:e58396.
https://doi.org/10.7554/eLife.58396
Further reading
-
- Cell Biology
- Genetics and Genomics
Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.
-
- Cell Biology
A combination of intermittent fasting and administering Wnt3a proteins to a bone injury can rejuvenate bone repair in aged mice.
