ArticleNature communications2018
Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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The trial behind it
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Who cites it
75 citing papers in PubMed, 112 citations in OpenAlex.
- Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The ubiquitin-proteasome system and autophagy as guardians of the cellular proteome.FEBS letters · 2026Review
- Discovery of Autophagy Modulators that Increase I1061T NPC1 Expression and Promote Cholesterol Efflux in Niemann-Pick Type C Patient-Derived Fibroblasts.ACS chemical biology · 2026Article
- Post-translational modifications of selective autophagy receptors: orchestrating cellular homeostasis, disease pathogenesis, and therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- MARCH6 Confers Protection Against Endoplasmic Reticulum Autophagy in Gliomas by Destabilizing FAM134B.Neurochemical research · 2026Article
- Advances in Research on Endoplasmic Reticulum-Associated Degradation Mechanisms in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2026Review
- Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells.Autophagy · 2026Article
- Membralin Assembles a MAN1B1-VCP Complex to Target Foreign Glycoproteins from the Endoplasmic Reticulum to Lysosomes for Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Genetic and Functional Evidence Links Germline Biallelic Inactivating Variants in WWOX to Histological Mixed-Type Thyroid Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adaptive Suppression of MAPT Transcription Maintains Tau Proteostasis in Developing Human Neurons.Research square · 2025Article
- Cholesterol sensing by the SCAP-FAM134B complex regulates ER-phagy and STING innate immunity.Nature cell biology · 2025Article
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- Exploration of Bromodomain Proteins as Drug Targets for Niemann-Pick Type C Disease.International journal of molecular sciences · 2025Article
- FAM134B in Cellular Homeostasis: Bridging Endoplasmic Reticulum-Phagy to Human Diseases.International journal of biological sciences · 2025Review
- Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.JCI insight · 2024Article
- Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.Journal of proteome research · 2024Article
- Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models.Cell death & disease · 2024Article
- Alterations in Proteostasis Mechanisms in Niemann-Pick Type C Disease.International journal of molecular sciences · 2024Review
- Autophagy of the ER: the secretome finds the lysosome.The FEBS journal · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Niemann-Pick type C disease is a fatal, progressive neurodegenerative disorder caused by loss-of-function mutations in NPC1, a multipass transmembrane glycoprotein essential for intracellular lipid trafficking. We sought to define the cellular machinery controlling degradation of the most common disease-causing mutant, I1061T NPC1. We show that this mutant is degraded, in part, by the proteasome following MARCH6-dependent ERAD. Unexpectedly, we demonstrate that I1061T NPC1 is also degraded by a recently described autophagic pathway called selective ER autophagy (ER-phagy). We establish the importance of ER-phagy both in vitro and in vivo, and identify I1061T as a misfolded endogenous substrate for this FAM134B-dependent process. Subcellular fractionation of I1061T Npc1 mouse tissues and analysis of human samples show alterations of key components of ER-phagy, including FAM134B. Our data establish that I1061T NPC1 is recognized in the ER and degraded by two different pathways that function in a complementary fashion to regulate protein turnover.
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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.