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
Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition.
Yuntao Bai,Jiyoung Kim,Bijay Bisunke,Laura A. Jayne,Josie A. Silvaroli,Michael S. Balzer,Megha Gandhi,Kevin M. Huang,Veronika Sander,Jason Prosek,Rachel E. Cianciolo,Sharyn D. Baker,Alex Sparreboom,Kenar D. Jhaveri,Katalin Susztak,Amandeep Bajwa,Navjotsingh Pabla +16 more
TL;DR: In this article, the authors investigated the underlying mechanisms of kidney toxicity and found that vemurafenib-associated kidney tubular epithelial cell dysfunction and kidney toxicity is BRAF-independent and caused by off-target ferrochelatase inhibition.
Journal ArticleDOI
Renal tubules transcriptome reveals metabolic maladaption during the progression of ischemia-induced acute kidney injury.
Difei Zhang,Yuexian Xing,Wenju Li,Fan Yang,Yue Lang,Jingping Yang,Zhihong Liu,Zhihong Liu,Zhihong Liu +8 more
TL;DR: This is the first study to charaterize renal tubule specific transcriptome during AKI progression and find dysregulation of multiple steps of lipid metabolism in tubule transcriptomes, shedding light on the molecular features in TECs for progressive AKI.
Posted ContentDOI
Instance segmentation of mitochondria in electron microscopy images with a generalist deep learning model
Ryan Conrad,Kedar Narayan +1 more
TL;DR: MitoNet, a DL model trained on mitochondrial instance segmentation data, which performs well on new and challenging volume EM benchmarks and an accompanying Python package and napari plugin, called empanada, can be used for efficient training, inference, and clean-up of instance segmentations on EM images.
Journal ArticleDOI
SQSTM1/p62 Controls mtDNA Expression and Participates in Mitochondrial Energetic Adaption via MRPL12.
TL;DR: SQSTM1/p62 is an important regulator of mtDNA expression machinery, which could effectively induce mt DNA expression and the effects were mediated by p38-dependent upregulation of mitochondrial ribosomal protein L12 (MRPL12) in renal tubular epithelial cells (TECs), a highly energy-demanding cell type related to OXPHOS.
Journal ArticleDOI
Single-cell mRNA profiling reveals changes in solute carrier expression and suggests a metabolic switch during zebrafish pronephros development.
Maximilian Schoels,Mingyue Zhuang,Andreas Fahrner,Sebastian Küchlin,Sagar,Henriette Franz,Annette Schmitt,Gerd Walz,Toma A. Yakulov +8 more
TL;DR: In this article, a single-cell RNA sequencing of zebrafish pronephric duct cells was performed to understand how the developing kidney responds to changes in filtered substrates and intrinsic energy requirements.
References
More filters
Journal ArticleDOI
Biochemistry and molecular cell biology of diabetic complications
TL;DR: This integrating paradigm provides a new conceptual framework for future research and drug discovery in diabetes-specific microvascular disease and seems to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain.
Book
Molecular Cell Biology
TL;DR: Molecular cell biology, Molecular cell biology , مرکز فناوری اطلاعات و اصاع رسانی, کδاوρزی
Journal ArticleDOI
Targeting HIF-1 for cancer therapy
TL;DR: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion.
Journal ArticleDOI
Oxidative stress and diabetic complications
TL;DR: Athrosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS.
Journal ArticleDOI
Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1
Zhidan Wu,Pere Puigserver,Ulf Andersson,Chen-Yu Zhang,Guillaume Adelmant,Vamsi K. Mootha,Amy E Troy,Saverio Cinti,Bradford B. Lowell,Richard C. Scarpulla,Bruce M. Spiegelman +10 more
TL;DR: PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs).