ArticleNature communications2023
C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy.
Article in Nature communications, 2023. 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, 32 citations in OpenAlex.
- VPS33A and VPS18 orchestrate porcine epidemic diarrhea virus replication by modulating autophagic flux.Virulence · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- The C9orf72/SMCR8 complex maintains microglial homeostasis via RAB8A-ESCRT-mediated lysosomal repair.The EMBO journal · 2026Article
- Regulatory mechanisms of post-translational modifications on autophagic flux in neurons following ischemic stroke.Molecular biology reports · 2026Review
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- Oxidative Stress and Lysosomal Dysfunction in Neurodegenerative Diseases: Underlying Mechanisms and Nanotherapeutic Targeting Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- From homeostasis to pathology, organelle-specific autophagy in skeletal muscle: a PRISMA-ScR scoping review.Frontiers in physiology · 2026Review
- The Rab7-Epg5 and Rab39-ema modules cooperatively position autophagosomes for efficient lysosomal fusions.eLife · 2025Article
- Bergeyella cardium variant induces a unique cytoplasmic vacuolization cell death floatptosis in macrophage.Cell discovery · 2025Article
- Vesicular transport in the autophagic route: RAB GTPases as pivotal regulators of autophagy.The Biochemical journal · 2025Review
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- Spatio-temporal processes in autophagosome-lysosome fusion.Medical review (2021) · 2025Review
- Mammalian nucleophagy: process and function.Autophagy · 2025Review
- Therapeutic Approaches for C9ORF72-Related ALS: Current Strategies and Future Horizons.International journal of molecular sciences · 2025Review
- Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery.Bioscience reports · 2025Review
- Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17.Nature communications · 2025Article
- Review
- Loss of the HOPS complex disrupts early-to-late endosome transition, impairs endosomal recycling and induces accumulation of amphisomes.Molecular biology of the cell · 2024Article
- Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multi-subunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is required for autophagosome-lysosome fusion in mammals, yet reconstituting the mammalian HOPS complex remains a challenge. Here we propose a "hook-up" model for mammalian HOPS complex assembly, which requires two HOPS sub-complexes docking on membranes via membrane-associated Rabs. We identify Rab39A as a key small GTPase that recruits HOPS onto autophagic vesicles. Proper pairing with Rab2 and Rab39A enables HOPS complex assembly between proteoliposomes for its tethering function, facilitating efficient membrane fusion. GTP loading of Rab39A is important for the recruitment of HOPS to autophagic membranes. Activation of Rab39A is catalyzed by C9orf72, a guanine exchange factor associated with amyotrophic lateral sclerosis and familial frontotemporal dementia. Constitutive activation of Rab39A can rescue autophagy defects caused by C9orf72 depletion. These results therefore reveal a crucial role for the C9orf72-Rab39A-HOPS axis in autophagosome-lysosome fusion.
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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.