Mitochondrial energetics in the kidney
Reads0
Chats0
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
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
Sirtuins in Renal Health and Disease
TL;DR: An overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology is provided, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets.
Journal ArticleDOI
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.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.
Eva Lonn,Jackie Bosch,Salim Yusuf,Patrick Sheridan,Janice Pogue,J. Malcolm O. Arnold,Catherine L. Ross,Andrew Arnold,Peter Sleight,Jeffrey L. Probstfield,Gilles R. Dagenais,Hope,Hope-Too Trial Investigators +12 more
TL;DR: In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.
Journal ArticleDOI
Functional and physical interaction between Bcl‐XL and a BH3‐like domain in Beclin‐1
M. Chiara Maiuri,Gaetane Le Toumelin,Alfredo Criollo,Alfredo Criollo,Alfredo Criollo,Jean-Christophe Rain,Fabien Gautier,Philippe Juin,Ezgi Tasdemir,Ezgi Tasdemir,Ezgi Tasdemir,Gérard Pierron,Kostoula Troulinaki,Nektarios Tavernarakis,John A. Hickman,Olivier Geneste,Guido Kroemer,Guido Kroemer,Guido Kroemer +18 more
TL;DR: A novel autophagy‐stimulatory function of BH3‐only proteins beyond their established role as apoptosis inducers is revealed and is revealed by competitively disrupting the interaction between Beclin‐1 and B cl‐2 or Bcl‐XL.
Journal ArticleDOI
Selective Mitochondrial Autophagy, or Mitophagy, as a Targeted Defense Against Oxidative Stress, Mitochondrial Dysfunction, and Aging
TL;DR: The term "mitophagy" is proposed to emphasize the non-random nature of the selective autophagy of mitochondria and may play a key role in retarding accumulation of somatic mutations of mtDNA with aging.
Journal ArticleDOI
Regulation of autophagy by ROS: physiology and pathology
TL;DR: Although connections between ROS and autophagy are observed in diverse pathological conditions, the mode of activation of Autophagy and its potential protective role remain incompletely understood and recent advances in the field of redox regulation of autophile focus on the role of mitochondria as a source of ROS and on mitophagy as a means for clearance of ROS.
Journal ArticleDOI
Nix is a selective autophagy receptor for mitochondrial clearance
Ivana Novak,Vladimir Kirkin,David G. McEwan,Ji Zhang,Philipp Wild,Alexis Rozenknop,Vladimir V. Rogov,Frank Löhr,Doris Popovic,Angelo Occhipinti,Andreas S. Reichert,Janoš Terzić,Volker Dötsch,Paul A. Ney,Ivan Dikic,Ivan Dikic +15 more
TL;DR: Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation, and ablation of the Nix:LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes.