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
Mitochondrial Dynamics and Metabolic Regulation.
Timothy Wai,Thomas Langer +1 more
TL;DR: The ways in which metabolic alterations convey changes in mitochondrial morphology and how disruption of mitochondrial morphology impacts cellular and organismal metabolism are reviewed.
Journal ArticleDOI
Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
Shireen A. Sarraf,Malavika Raman,Virginia Guarani-Pereira,Mathew E. Sowa,Edward L. Huttlin,Steven P. Gygi,J. Wade Harper +6 more
TL;DR: Structural and topological analysis revealed extensive conservation of PARKIN-dependent ubiquitylation sites on cytoplasmic domains in vertebrate and Drosophila melanogaster MOM proteins, providing a resource for understanding how the PINK1–PARKIN pathway re-sculpts the proteome to support mitochondrial homeostasis.
OtherDOI
Pathophysiology of Acute Kidney Injury
TL;DR: The successful recovery from AKI depends on the degree to which repair processes ensue and these may be compromised in elderly or chronic kidney disease (CKD) patients, so targeting the extension phase of treatment with the greatest possible impact is suggested.
Journal ArticleDOI
Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease
Dick de Zeeuw,Tadao Akizawa,Paul Audhya,George L. Bakris,Melanie P. Chin,Heidi Christ-Schmidt,Angie Goldsberry,Mark Houser,Melissa Krauth,Hiddo J.L. Heerspink,John J.V. McMurray,Colin J. Meyer,Hans-Henrik Parving,G. Remuzzi,Robert D. Toto,Nosratola D. Vaziri,Christoph Wanner,Janet Wittes,Danielle Wrolstad,Glenn M. Chertow +19 more
TL;DR: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of end-stage renal disease (ESRD) or death from cardiovascular causes and was terminated on the recommendation of the independent data and safety monitoring committee.
Journal ArticleDOI
Metabolic regulation of mitochondrial dynamics
Prashant Mishra,David C. Chan +1 more
TL;DR: This work reviews the dynamic properties of mitochondria, with an emphasis on how these processes respond to cellular signaling events and how they affect metabolism.