ArticleThe Journal of clinical investigation2021
Targeting a Braf/Mapk pathway rescues podocyte lipid peroxidation in CoQ-deficiency kidney disease.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- Zhuangyang Bushen Pill Attenuates Renal Injury in Chronic Glomerulonephritis by Suppressing the MAPK Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Elovl7 sensitizes podocytes to ferroptosis in podocytopathy by elongating polyunsaturated fatty acids.Cell death & disease · 2025Article
- Benchmarking large language models for cell typing in single-cell RNA-Seq.Briefings in bioinformatics · 2025Article
- Dysregulated Anaerobic Glycolysis in Podocytes is Relevant to the Progression of Focal Segmental Glomerulosclerosis.Kidney international reports · 2025Article
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- Profiling with senescence-associated secretory phenotype score identifies GDC-0879 as a small molecule sensitizing glioblastoma to anti-PD1.Cell death & disease · 2025Article
- Metabolic reprogramming by endothelial ANGPTL4 depletion protects against diabetic kidney disease.bioRxiv : the preprint server for biology · 2025Article
- Transcriptional Regulators YAP and TAZ Have Distinct Abilities to Compensate for One Another in Podocytes.Journal of the American Society of Nephrology : JASN · 2025Article
- Coenzyme QFree radical biology & medicine · 2025Article
- Expanding the clinical spectrum of 19p13.3 microduplication syndrome: a case report highlighting nephrotic syndrome and literature review.BMC pediatrics · 2025Review
- Evaluation of urine glutathione peroxidase 4 in cats with chronic kidney disease.Frontiers in veterinary science · 2025Article
- Understanding coenzyme Q.Physiological reviews · 2024Review
- starTracer is an accelerated approach for precise marker gene identification in single-cell RNA-Seq analysis.Communications biology · 2024Article
- Organelle communication maintains mitochondrial and endosomal homeostasis during podocyte lipotoxicity.JCI insight · 2024Article
- Mechanisms of Abnormal Lipid Metabolism in the Pathogenesis of Disease.International journal of molecular sciences · 2024Review
- Comprehensive analysis of the endothelin system in the kidneys of mice, rats, and humans.Bioscience reports · 2024Article
- Targeting the transmembrane cytokine co-receptor neuropilin-1 in distal tubules improves renal injury and fibrosis.Nature communications · 2024Article
- Article
- Prenyl diphosphate synthase subunit 2 is downregulated in abdominal aortic aneurysm and retards the progression of abdominal aortic aneurysm.CytoJournal · 2024Article
- Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis.Kidney diseases (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations affecting mitochondrial coenzyme Q (CoQ) biosynthesis lead to kidney failure due to selective loss of podocytes, essential cells of the kidney filter. Curiously, neighboring tubular epithelial cells are spared early in disease despite higher mitochondrial content. We sought to illuminate noncanonical, cell-specific roles for CoQ, independently of the electron transport chain (ETC). Here, we demonstrate that CoQ depletion caused by Pdss2 enzyme deficiency in podocytes results in perturbations in polyunsaturated fatty acid (PUFA) metabolism and the Braf/Mapk pathway rather than ETC dysfunction. Single-nucleus RNA-Seq from kidneys of Pdss2kd/kd mice with nephrotic syndrome and global CoQ deficiency identified a podocyte-specific perturbation of the Braf/Mapk pathway. Treatment with GDC-0879, a Braf/Mapk-targeting compound, ameliorated kidney disease in Pdss2kd/kd mice. Mechanistic studies in Pdss2-depleted podocytes revealed a previously unknown perturbation in PUFA metabolism that was confirmed in vivo. Gpx4, an enzyme that protects against PUFA-mediated lipid peroxidation, was elevated in disease and restored after GDC-0879 treatment. We demonstrate broader human disease relevance by uncovering patterns of GPX4 and Braf/Mapk pathway gene expression in tissue from patients with kidney diseases. Our studies reveal ETC-independent roles for CoQ in podocytes and point to Braf/Mapk as a candidate pathway for the treatment of kidney diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.