Drp1S600 phosphorylation regulates mitochondrial fission and progression of nephropathy in diabetic mice

Phosphorylation of dynamin-related protein 1 (Drp1) represents an important regulatory mechanism for mitochondrial fission. Here, we established the role of Drp1 serine 600 (Drp1S600) phosphorylation in mitochondrial fission in vivo and assessed the functional consequences of targeted elimination of the Drp1S600 phosphorylation site in the 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 dependent but not cell type dependent. Mechanistically, we show that mitochondrial fission in high-glucose conditions occurs through concomitant binding of phosphorylated 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 the idea 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 in mitochondrial dynamics.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

Related Links:

Source: ClinicoEconomics and Outcomes Research - Category: Health Management Tags: ClinicoEconomics and Outcomes Research Source Type: research
DiscussionWe estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Arbutin protects HK-2 cells against high glucose-induced apoptosis and autophagy by up-regulating microRNA-27a. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2940-2947 Authors: Lv L, Zhang J, Tian F, Li X, Li D, Yu X Abstract Arbutin (ARB) has been widely used in skin pigmentation disorders. Nevertheless, the involvements of ARB in diabetic nephropathy (DN) are still unknown. We investigated the functions of ARB in high glucose (HG)-induced cell apoptosis and autophagy in HK-2 cells. Cell viability was examined through CCK-8 in HK-2 cells after disposal with 45 mM glucose and ARB (10-50&th...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
This study elucidates the potential to use mitochondria from different donors (PAMM) to treat UVR stress and possibly other types of damage or metabolic malfunctions in cells, resulting in not only in-vitro but also ex-vivo applications. Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression https://www.fightaging.org/archives/2019/07/gene-therapy-in-mice-alters-the-balance-of-macrophage-phenotypes-to-slow-atherosclerosis-progression/ Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 20 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Tina Hörbelt, Birgit Knebel, Pia Fahlbusch, David Barbosa, Daniella Herzfeld de Wiza, Frederique Van de Velde, Yves Van Nieuwenhove, Bruno Lapauw, G. Hege Thoresen, Hadi Al-Hasani, Dirk Müller-Wieland, D. Margriet Ouwens, Jorg KotzkaAbstractSecreted frizzled-related protein (sFRP) 4 is an adipokine with increased expression in white adipose tissue from obese subjects with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Yet, it is unknown whether sFRP4 action contributes ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Publication date: Available online 20 July 2019Source: Journal of Trace Elements in Medicine and BiologyAuthor(s): Nikolay Solovyev, Frank Vanhaecke, Bernhard MichalkeAbstractDiabetes mellitus is a chronic metabolic disease caused by insulin deficiency (type I) or dysfunction (type II). Diabetes is a threatening public health concern. It is considered as one of the priority non-communicable diseases, due to its high and increasing incidence, the associated healthcare costs, and threatening medical complications. Two trace elements selenium (Se) and iodine (I) were intensively discussed in the context of diabetic pathology ...
Source: Journal of Trace Elements in Medicine and Biology - Category: Biochemistry Source Type: research
CONCLUSION: Cranial MRI should be performed to identify the presence of brain abscesses in elderly patients with K. pneumoniae bloodstream infections but without clinically evident neurological signs or symptoms. Serial MRI studies are important to monitor the therapeutic course. PMID: 31321760 [PubMed - in process]
Source: Acta Neurologica Taiwanica - Category: Neurology Tags: Acta Neurol Taiwan Source Type: research
CONCLUSIONSRYGB offers sustained, long-term weight loss with significant resolution of major comorbidities in older veterans, with acceptably low morbidity and mortality.
Source: The American Journal of Surgery - Category: Surgery Source Type: research
This article focuses on the common diabetes related infections in the Head and Neck region of the body. Some of the life threatening infections like malignant otitis externa and rhino-cerebral mucormycosis affect this region of body. PMID: 31321937 [PubMed - in process]
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
Authors: Gupta P, Gupta R, Gupta AK Abstract The chronic complications of Diabetes Mellitus (DM), which may be present in as many as 50% of the patients at the time of diagnosis, are a major burden for both individuals with the disease and health systems and it has been estimated that as much as 60-70% of healthcare expenditure related to diabetes (about 670 billion dollars a year) is currently attributable to chronic complications of the disease. These high prevalence rates are widely acknowledged to further rise as poor lifestyle choices and their consequences continue to rise. Adding to that is an aging populati...
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
More News: Biomedical Science | Diabetes | Endocrinology | Mitochondria