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.
Pubmed ID: 31063459 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets DLP1
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Synaptopodin
View all literature mentionsThis monoclonal targets SDHA
View all literature mentionsThis polyclonal targets Cofilin
View all literature mentionsThis monoclonal targets ARP3
View all literature mentionsThis polyclonal targets Human Arp2, C Terminus
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets ACTR3
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets translocase of outer mitochondrial membrane 20 (TOMM20)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets DRP1 (phospho-Ser637)
View all literature mentionsThis polyclonal targets Cofilin 1 + 2 antibody
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets native GFP from Aequorea victoria
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets mitochondrial fission factor
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsSoftware for identifying, characterizing, and quantifying proteins in biological samples. Can be used for range of proteomics workflows such as protein and peptide identification, PTM analysis, and isobaric mass tagging for quantification. Supports multiple database search algorithms and multiple dissociation techniques.
View all literature mentionsAMT camera system software that performs digital image acquisition, processing, and storage. An operations manual and software specifications are available on the main site.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsCollection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsAMT camera system software that performs digital image acquisition, processing, and storage. An operations manual and software specifications are available on the main site.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsSoftware for identifying, characterizing, and quantifying proteins in biological samples. Can be used for range of proteomics workflows such as protein and peptide identification, PTM analysis, and isobaric mass tagging for quantification. Supports multiple database search algorithms and multiple dissociation techniques.
View all literature mentionsCollection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis monoclonal targets DLP1
View all literature mentions