ArticleThe Journal of clinical investigation2019
Drp1S600 phosphorylation regulates mitochondrial fission and progression of nephropathy in diabetic mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- Advances in understanding the role of mitochondria in renal ischemia-reperfusion injury.Clinical and experimental nephrology · 2025Review
- DeSUMOylation of RBMX regulates exosomal sorting of cargo to promote renal tubulointerstitial fibrosis in diabetic kidney disease.Journal of advanced research · 2025Article
- Emerging insights into pulmonary hypertension: the potential role of mitochondrial dysfunction and redox homeostasis.Molecular and cellular biochemistry · 2025Review
- mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction.Experimental & molecular medicine · 2025Article
- Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Mitochondrial Dysfunction and Immune Cell Infiltration in Diabetic Kidney Disease: A Mendelian Randomization and Multiomics Study.Mediators of inflammation · 2025Article
- Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior.iScience · 2024Article
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- NDUFS4 regulates cristae remodeling in diabetic kidney disease.Nature communications · 2024Article
- Effects of phosphorylation on Drp1 activation by its receptors, actin, and cardiolipin.Molecular biology of the cell · 2024Article
- Glutamine Metabolism Promotes Renal Fibrosis through Regulation of Mitochondrial Energy Generation and Mitochondrial Fission.International journal of biological sciences · 2024Article
- Renal Epithelial Mitochondria: Implications for Hypertensive Kidney Disease.Comprehensive Physiology · 2023Article
- Glycyrrhizic Acid Protects Glomerular Podocytes Induced by High Glucose by Modulating SNARK/AMPK Signaling Pathway.Current medical science · 2023Article
- Molecular pathways that drive diabetic kidney disease.The Journal of clinical investigation · 2023Review
- Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells.World journal of stem cells · 2022Article
- Sestrin2 remedies podocyte injury via orchestrating TSP-1/TGF-β1/Smad3 axis in diabetic kidney disease.Cell death & disease · 2022Article
- Mitochondria dysfunction in Charcot Marie Tooth 2B Peripheral Sensory Neuropathy.Communications biology · 2022Article
- Mechanisms of podocyte injury and implications for diabetic nephropathy.Clinical science (London, England : 1979) · 2022Article
- Mitochondrial quality control in diabetic cardiomyopathy: from molecular mechanisms to therapeutic strategies.International journal of biological sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Phosphorylation of Dynamin-related protein1 (Drp1) represents an important regulatory mechanism for mitochondrial fission. Here we established the role of Drp1 Serine 600 (S600) phosphorylation on mitochondrial fission in vivo, and assessed the functional consequences of targeted elimination of the Drp1S600 phosphorylation site in progression of diabetic nephropathy (DN). We generated a knockin mouse in which S600 was mutated to alanine (Drp1S600A). We found that diabetic Drp1S600A mice exhibited improved biochemical and histological features of DN along with reduced mitochondrial fission and diminished mitochondrial ROS in vivo. Importantly, we observed that the effect of Drp1S600 phosphorylation on mitochondrial fission in the diabetic milieu was stimulus- but not cell type-dependent. Mechanistically, we showed that mitochondrial fission in high glucose conditions occurs through concomitant binding of phospho-Drp1S600 with mitochondrial fission factor (Mff) and actin-related protein 3 (Arp3), ultimately leading to accumulation of F-actin and Drp1 on the mitochondria. Taken together, these findings establish that a single phosphorylation site in Drp1 can regulate mitochondrial fission and progression of DN in vivo, and highlight the stimulus-specific consequences of Drp1S600 phosphorylation on mitochondrial dynamics.
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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.