ArticleEMBO reports2024
ER-to-lysosome-associated degradation acts as failsafe mechanism upon ERAD dysfunction.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Remaking an exit: dynamic regulation of ER exit sites by post-translational modifications.Trends in cell biology · 2026Review
- Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.FEBS open bio · 2026Article
- The ubiquitin-proteasome system and autophagy as guardians of the cellular proteome.FEBS letters · 2026Review
- Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity.Neuron · 2026Article
- Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.Cellular & molecular biology letters · 2026Review
- SEL1L-HRD1 ERAD-autophagy interplay maintains mitochondrial homeostasis in brown adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- FAM134B controls collagen I dynamics in hepatic stellate cell-driven fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- A small molecule VDAC ligand inhibits ERAD and induces selective cancer cell death via disruption of calcium homeostasis.Nature communications · 2026Article
- Tripartite motif 13 orchestrates endoplasmic reticulum-associated degradation and endoplasmic reticulum-phagy to modulate dendritic cell-mediated immune responses in sepsis.Burns & trauma · 2026Article
- The role of N-glycans and their processing in ER-to-lysosome-associated degradation of disease-causing mutant Neuroserpin.Autophagy reports · 2026Article
- Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation.bioRxiv : the preprint server for biology · 2025Article
- The Glymphatic System and Diaphragmatic Dysfunction in Patients with Chronic Obstructive Pulmonary Disease and Chronic Heart Failure: The Importance of Inspiratory Rehabilitation Training.Journal of cardiovascular development and disease · 2025Review
- Liver CYP4A autophagic lysosomal degradation: A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site.Molecular pharmacology · 2025Article
- The intrinsically disordered regions of organellophagy receptors are interchangeable and control organelle fragmentation, ER-phagy and mitophagy flux.Nature cell biology · 2025Article
- Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity.bioRxiv : the preprint server for biology · 2025Article
- N-palmitoyl glycine mediates depression-associated atrial fibrillation via Man1a2-dependent autophagy and NRAP dysregulation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Glycosylation Regulation by TMEM230 in Aging and Autoimmunity.International journal of molecular sciences · 2025Article
- Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway.Open life sciences · 2025Article
- CNX:FAM134B-driven ERLAD of ATZ polymers proceeds via enhanced formation of VAPA:ORP1L:RAB7 contact sites between ER and endolysosomes.Autophagy reports · 2025Article
- Enhancing Tissue Factor Production: The Role of N-Glycosylation and ERAD Pathway Modulation.Protein and peptide letters · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The endoplasmic reticulum (ER) produces proteins destined to organelles of the endocytic and secretory pathways, the plasma membrane, and the extracellular space. While native proteins are transported to their intra- or extracellular site of activity, folding-defective polypeptides are retro-translocated across the ER membrane into the cytoplasm, poly-ubiquitylated and degraded by 26 S proteasomes in a process called ER-associated degradation (ERAD). Large misfolded polypeptides, such as polymers of alpha1 antitrypsin Z (ATZ) or mutant procollagens, fail to be dislocated across the ER membrane and instead enter ER-to-lysosome-associated degradation (ERLAD) pathways. Here, we show that pharmacological or genetic inhibition of ERAD components, such as the α1,2-mannosidase EDEM1 or the OS9 ERAD lectins triggers the delivery of the canonical ERAD clients Null Hong Kong (NHK) and BACE457Δ to degradative endolysosomes under control of the ER-phagy receptor FAM134B and the LC3 lipidation machinery. Our results reveal that ERAD dysfunction is compensated by the activation of FAM134B-driven ERLAD pathways that ensure efficient lysosomal clearance of orphan ERAD clients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.