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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Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment.
TL;DR: More mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.
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Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance.
Meng Zhao,Yizhuo Wang,Ling Li,Shuyun Liu,Chengshi Wang,Yujia Yuan,Guang Yang,Younan Chen,Jingqiu Cheng,Yanrong Lu,Jingping Liu +10 more
TL;DR: In this article, the authors investigated the specific role of mtROS in initiating mitochondrial DNA (mtDNA) damage and inflammation during IRI-AKI, and they found that mt-ROS can promote renal injury by suppressing TFAM-mediated mtDNA maintenance, resulting in decreased mitochondrial energy metabolism and increased cytokine release.
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Mitochondrial quality control in kidney injury and repair.
Chengyuan Tang,Juan Cai,Xiao Ming Yin,Joel M. Weinberg,Manjeri A. Venkatachalam,Zheng Dong,Zheng Dong +6 more
TL;DR: The role of mitochondrial quality control mechanisms in kidney injury and repair is discussed and their potential as therapeutic targets are highlighted.
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Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities
Lucas Opazo-Ríos,Sebastian Mas,Gema Marín-Royo,Sergio Mezzano,Carmen Gomez-Guerrero,Juan Antonio Moreno,Jesús Egido +6 more
TL;DR: This review examines the recent preclinical and clinical research about the potentially harmful effects of lipid effects in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity.
References
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