ArticleAnnals of the rheumatic diseases2014
HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE.
Article in Annals of the rheumatic diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 3 of them syntheses that pooled it.
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Who cites it
114 citing papers in PubMed, 3 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review.Frontiers in immunology · 2019Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial.Lancet (London, England) · 2018Trial
- Geranylgeranylation is required for B-cell proliferation and plasma cell survival implications for autoimmune therapy.Cellular & molecular immunology · 2026Article
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- CD4 + T cell-derived exosomal miR-223-3p serves as a potential biomarker for systemic lupus erythematosus and attenuates lupus nephritis in NZBWF1/J mice.Journal of nanobiotechnology · 2026Article
- T-Cell Immunosenescence in Systemic Lupus Erythematosus: Molecular Mechanisms and Therapeutic Perspectives.Clinical reviews in allergy & immunology · 2026Review
- Mitophagy and Immune Infiltration in Primary Sjögren's Disease: Insights from Bioinformatics Analysis.International journal of molecular sciences · 2026Article
- Mitochondrial dysfunction drives natural killer cell dysfunction in systemic lupus erythematosus.JCI insight · 2026Article
- Tmem110 regulates the conformation of TRPML1 to maintain endolysosomal homeostasis and prevent mitochondrial DNA leakage and pathological self-DNA processing.Nature communications · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus.Cell reports · 2025Article
- Association of Mitochondrial DNA Haplogroups with Pediatric Systemic Lupus Erythematosus Disease Activity, Damage Scores, and Lupus Nephritis.Journal of clinical medicine · 2025Article
- A TLR7/9-IFNα-LDHB axis drives vital NET release and compromises antibacterial defense in lupus.bioRxiv : the preprint server for biology · 2025Article
- IgG and IgM Anti-Phosphatidylserine/Prothrombin Complex Antibody Detection May Improve Classification Accuracy of Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome.ACR open rheumatology · 2025Article
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- Article
- RAB4A DRIVES PROINFLAMMATORY CD4Research square · 2025Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveAccumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupus-prone mice.
methodsMitochondria were evaluated in peripheral blood lymphocytes (PBL) of 38 SLE patients and 21 healthy controls and mouse models by flow cytometry, microscopy and western blot. MRL/lpr mice were treated with 125 μg/kg 3-PEHPC or 1 mg/kg rapamycin for 10 weeks, from 4 weeks of age. Disease was monitored by antinuclear antibody (ANA) production, proteinuria, and renal histology.
resultsOverexpression of HRES-1/Rab4 increased the mitochondrial mass of PBL (1.4-fold; p=0.019) and Jurkat cells (2-fold; p=0.000016) and depleted the mitophagy initiator protein Drp1 both in human (-49%; p=0.01) and mouse lymphocytes (-41%; p=0.03). Drp1 protein levels were profoundly diminished in PBL of SLE patients (-86±3%; p=0.012). T cells of 4-week-old MRL/lpr mice exhibited 4.7-fold over-expression of Rab4A (p=0.0002), the murine homologue of HRES-1/Rab4, and depletion of Drp1 that preceded the accumulation of mitochondria, ANA production and nephritis. 3-PEHPC increased Drp1 (p=0.03) and reduced mitochondrial mass in T cells (p=0.02) and diminished ANA production (p=0.021), proteinuria (p=0.00004), and nephritis scores of lupus-prone mice (p<0.001).
conclusionsThese data reveal a pathogenic role for HRES-1/Rab4-mediated Drp1 depletion and identify endocytic control of mitophagy as a treatment target in SLE.
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