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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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
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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 Article
Acute renal failure in the new millennium: time to consider combination therapy.
TL;DR: Clinical studies should employ very specific definitions of ARF, outcomes evaluated, indications for renal replacement therapy, and severity of illness evaluation methods, and aggressive preventative measures will significantly improve the incidence and outcome of ARf in the 21st century.
Journal ArticleDOI
OPA1 (Kjer Type) Dominant Optic Atrophy: A Novel Mitochondrial Disease
TL;DR: The findings that OPA1-type DOA, as Leber optic neuropathy, is caused by the impairment of a mitochondrial protein address the question of the vulnerability of the retinal ganglion cell in response to mitochondrial defects.
Journal ArticleDOI
Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury.
Masayuki Ishihara,Madoka Urushido,Kazu Hamada,Tatsuki Matsumoto,Yoshiko Shimamura,Koji Ogata,Kosuke Inoue,Yoshinori Taniguchi,Taro Horino,Mikiya Fujieda,Shimpei Fujimoto,Yoshio Terada +11 more
TL;DR: Observations demonstrate that autophagy is induced in renal tubules by at least two independent pathways involving p53-sestrin-2 and HIF-1α-BNIP3, which may be activated by different types of stress to protect the renal tubule during AKI.
Journal ArticleDOI
Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels
Arnaud Mourier,Elisa Motori,Tobias Brandt,Marie Lagouge,Ilian Atanassov,Anne Galinier,Gunter Rappl,Susanne Brodesser,Kjell Hultenby,Christoph Dieterich,Nils-Göran Larsson,Nils-Göran Larsson +11 more
TL;DR: Mitofusin 2 plays an unexpected role in maintaining the terpenoid biosynthesis pathway and is necessary for mitochondrial coenzyme Q biosynthesis.
Journal ArticleDOI
Glutathione peroxidase-1 regulates mitochondrial function to modulate redox-dependent cellular responses.
Diane E. Handy,Edith Lubos,Yi Yang,John D. Galbraith,Neil J. Kelly,Ying-Yi Zhang,Jane A. Leopold,Joseph Loscalzo +7 more
TL;DR: GPx-1 can modulate redox-dependent cellular responses by regulating mitochondrial function by decreasing mitochondrial oxidants, and data suggest that alterations in GPx- 1 can attenuate cell proliferation.