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Open AccessJournal ArticleDOI

Mitochondrial energetics in the kidney

Pallavi Bhargava, +1 more
- 01 Oct 2017 - 
- Vol. 13, Iss: 10, pp 629-646
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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.

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Citations
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Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance.

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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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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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Journal ArticleDOI

Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and early fibrosis.

TL;DR: It is proposed that mitochondrial dysfunction induced by AKI is a persistent cellular injury that promotes progression to fibrosis and CKD, and that this model can be used to test mitochondrial therapeutics that limit progression to collagen deposition and fibrosis.
Journal ArticleDOI

Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission.

TL;DR: Structure–function analyses driven by a crystal structure of the cytosolic domain of the Drp1 receptor MiD51 reveals a nucleotidyltransferase fold and nucleotide binding activity that is independent of itsDrp1 binding activity.
Journal ArticleDOI

Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule–specific knockout mouse models

TL;DR: Two Bax-deficient mouse models are examined and a critical role of Bax and Bak in tubular cell apoptosis in ischemic acute kidney is supported, and necrosis and apoptosis have distinguishable regulatory functions.
Journal ArticleDOI

Renoprotective approaches and strategies in acute kidney injury.

TL;DR: This review proposes experimental strategies for the identification of renoprotective agents or methods with clinical potential in acute kidney injury and proposes the consideration of combination therapy by targeting multiple targets in AKI.
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