Mitochondrial energetics in the kidney
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TLDR
Implementing compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus and inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.Abstract:
The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.read more
Citations
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Journal Article
Risk factors and outcome of hospital-acquired acute renal failure (clinical epidemiologic study).
Mortagy Ak,Radwan M,Gadallah M +2 more
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Sepsis-Associated Acute Kidney Injury.
TL;DR: In this article, the authors discuss the current understanding of S-AKI, recent advances in pathophysiology and biomarker development, and current preventive and therapeutic approaches, and present several biomarkers have been developed in an attempt to improve diagnostic sensitivity and specificity of SAKI.
Journal ArticleDOI
Drp1S600 phosphorylation regulates mitochondrial fission and progression of nephropathy in diabetic mice
Daniel L. Galvan,Jianyin Long,Nathanael Green,Nathanael Green,Benny H. Chang,Benny H. Chang,Jamie S. Lin,Paul T. Schumacker,Luan D. Truong,Paul A. Overbeek,Farhad R. Danesh,Farhad R. Danesh +11 more
TL;DR: It is established that a single phosphorylation site in Drp1 can regulate mitochondrial fission and progression of DN in vivo, and the stimulus-specific consequences of Drp2 Serine 600 phosphorylations on mitochondrial dynamics are highlighted.
Journal ArticleDOI
Numb Depletion Promotes Drp1-Mediated Mitochondrial Fission and Exacerbates Mitochondrial Fragmentation and Dysfunction in Acute Kidney Injury
Ze Liu,Hao Li,Jianqun Su,Shihui Xu,Fengxin Zhu,Jun Ai,Zheng Hu,Miaomiao Zhou,Jianwei Tian,Zhiyuan Su,Peiliang Yang,Jing Nie +11 more
TL;DR: It is suggested that Numb depletion promotes mitochondrial fragmentation by promoting the phosphorylation of Drp1 Ser637 and thus exacerbates cisplatin-induced mitochondrial dysfunction and tubular cell apoptosis and adds a novel insight into modulating mechanism of mitochondrial dynamics during AKI.
Journal ArticleDOI
An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank.
Ekaterina Yonova-Doing,Ekaterina Yonova-Doing,Claudia Calabrese,Aurora Gomez-Duran,Aurora Gomez-Duran,Katherine Schon,Wei Wei,Savita Karthikeyan,Patrick F. Chinnery,Joanna M M Howson,Joanna M M Howson +10 more
TL;DR: In this article, the UK Biobank identified 227 new associations between mtDNA variants and phenotypes and established a reference atlas of mtDNA-phenotype associations, including rs2853822 /m.8655c>T (MT-ATP6) with type 2 diabetes, rs878966690 /m.13117c>A>G(MT-ND5) with multiple sclerosis, 6 mtDNA associations with adult height, 24 mt DNA associations with 2 liver biomarkers and 16 mtDNA association with parameters of renal function.
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