ArticleAutophagy2023
RAB21 controls autophagy and cellular energy homeostasis by regulating retromer-mediated recycling of SLC2A1/GLUT1.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Functionalized Fluorescent Nanodiamonds Reveal Therapeutic Protein Clearance Through ENDOTAC Linked to AUTOTAC.Advanced healthcare materials · 2026Article
- Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration.Translational neurodegeneration · 2026Article
- PCOS combined with obesity aggravates the metabolic and immune abnormality in females.BMC women's health · 2026Article
- IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K/Akt/mTOR Pathway to Regulate Autophagy.Cancer science · 2026Article
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Ginsenoside Rg5 inhibits colorectal cancer, at least partially by blocking the lysosomal degradation of colorectal cancer cells.Scientific reports · 2026Article
- Autophagy inhibition in intestinal stem cells favors enteroendocrine cell differentiation through Stat92E activity.Disease models & mechanisms · 2025Article
- Vesicular transport in the autophagic route: RAB GTPases as pivotal regulators of autophagy.The Biochemical journal · 2025Review
- The Biological Role and Clinical Significance of BECLIN-1 in Cancer.International journal of molecular sciences · 2025Review
- The circRNA-mediated ceRNA molecular regulatory network in fatigue-type type 2 diabete.Journal of translational medicine · 2025Article
- Proteomics analysis reveals elevated RAB21 in serum-derived extracellular vesicles from patients with follicular thyroid carcinoma.Oncology letters · 2025Article
- Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation.Nature communications · 2025Article
- Delineating cysteine-reactive compound modulation of cellular proteostasis processes.Nature chemical biology · 2025Article
- The link between the trans-Golgi network and tumour progression.Molecular biology reports · 2025Review
- The interrelated roles of RAB family proteins in the advancement of neoplastic growth.Frontiers in oncology · 2025Review
- Multi-omics analysis reveals lysosome-associated molecular subtype characterization and prognostic modeling system in lung adenocarcinoma.Journal of Cancer · 2025Article
- Development of Diagnostic and Predictive Models for COPD Based on Anoikis Resistance.Journal of inflammation research · 2025Article
- A new role of RAB21 and VARP in autophagy and autophagic exocytosis of ATP.Autophagy reports · 2025Article
- Rab21 recruits EEA1 and competes with Rab5 for Rabex-5 activation.Frontiers in cell and developmental biology · 2025Article
- Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.Cancers · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endosomal system maintains cellular homeostasis by coordinating multiple vesicular trafficking events, and the retromer complex plays a critical role in endosomal cargo recognition and sorting. Here, we demonstrate an essential role for the small GTPase RAB21 in regulating retromer-mediated recycling of the glucose transporter SLC2A1/GLUT1 and macroautophagy/autophagy. RAB21 depletion mis-sorts SLC2A1 to lysosomes and affects glucose uptake, thereby activating the AMPK-ULK1 pathway to increase autophagic flux. RAB21 depletion also increases lysosome function. Notably, RAB21 depletion does not overtly affect retrograde transport of IGF2R/CI-M6PR or WLS from endosomes to the trans-Golgi network. We speculate that RAB21 regulates fission of retromer-decorated endosomal tubules, as RAB21 depletion causes accumulation of the SNX27-containing retromer complex on enlarged endosomes at the perinuclear region. Functionally, RAB21 depletion sensitizes cancer cells to energy stress and inhibits tumor growth in vivo, suggesting an oncogenic role for RAB21. Overall, our study illuminates the role of RAB21 in regulating endosomal dynamics and maintaining cellular energy homeostasis and suggests RAB21 as a potential metabolic target for cancer therapy.
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