The Mitochondria-Targeted Metabolic Tubular Injury in Diabetic Kidney Disease

Jiang, Hong; Shao, Xue; Sha, Jingquan; Qu, Lihui; Weng, Chunhua; Shen, Xiaohua; Wang, Yucheng; Huang, Hongfeng; Wang, Yingying; Wang, Cuili; Feng, Shi Ting; Wang, Meizhen; Feng, Huajun; Geekiyanage, Sudarshanee; Davidson, Alan J.; Chen, Jianghua

doi:10.33594/000000011

Cited by 50 publications

(43 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are consistent with a recent observation that MetS patients with CKD (Jiang et al, 2019) have increased apoptosis and impaired ΔΨm in renal tubules but not podocytes (Jiang et al, 2019). Furthermore, oxidative stressmediated perturbance of glycolysis and tricarboxylic acid cycle contributes to the tubular injury in MetS (Jiang et al, 2019). The injury in human renal proximal tubule cells caused by highglucose in the medium is reversed by the mitochondria-targeted antioxidant, MitoQ (Xiao M. et al, 2017), that is related to the restoration of the Nrf2 expression, inhibition of the expression of Kelch-like ECH-associated protein (Keap1), and the interaction between Nrf2 and Keap1 (Xiao L et al, 2017).…”

Section: Renal Dysfunction In Metabolic Syndromesupporting

confidence: 94%

“…Metabolomics analysis demonstrated that the suppression of mitochondrial metabolism and activity in patients with MetS is associated with lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis) and less mitochondria DNA and protein content in the kidney ( Sharma et al, 2013 ). These findings are consistent with a recent observation that MetS patients with CKD ( Jiang et al, 2019 ) have increased apoptosis and impaired ΔΨm in renal tubules but not podocytes ( Jiang et al, 2019 ). Furthermore, oxidative stress-mediated perturbance of glycolysis and tricarboxylic acid cycle contributes to the tubular injury in MetS ( Jiang et al, 2019 ).…”

Section: Renal Dysfunction In Metabolic Syndromesupporting

confidence: 93%

See 1 more Smart Citation

Coordinated Contribution of NADPH Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Metabolic Syndrome and Its Implication in Renal Dysfunction

Lee

José

2021

Front. Pharmacol.

View full text Add to dashboard Cite

Metabolic syndrome (MetS), a complex of interrelated risk factors for cardiovascular disease and diabetes, is comprised of central obesity (increased waist circumference), hyperglycemia, dyslipidemia (high triglyceride blood levels, low high-density lipoprotein blood levels), and increased blood pressure. Oxidative stress, caused by the imbalance between pro-oxidant and endogenous antioxidant systems, is the primary pathological basis of MetS. The major sources of reactive oxygen species (ROS) associated with MetS are nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases and mitochondria. In this review, we summarize the current knowledge regarding the generation of ROS from NADPH oxidases and mitochondria, discuss the NADPH oxidase- and mitochondria-derived ROS signaling and pathophysiological effects, and the interplay between these two major sources of ROS, which leads to chronic inflammation, adipocyte proliferation, insulin resistance, and other metabolic abnormalities. The mechanisms linking MetS and chronic kidney disease are not well known. The role of NADPH oxidases and mitochondria in renal injury in the setting of MetS, particularly the influence of the pyruvate dehydrogenase complex in oxidative stress, inflammation, and subsequent renal injury, is highlighted. Understanding the molecular mechanism(s) underlying MetS may lead to novel therapeutic approaches by targeting the pyruvate dehydrogenase complex in MetS and prevent its sequelae of chronic cardiovascular and renal diseases.

show abstract

Section: Renal Dysfunction In Metabolic Syndromesupporting

confidence: 94%

Section: Renal Dysfunction In Metabolic Syndromesupporting

confidence: 93%

Coordinated Contribution of NADPH Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Metabolic Syndrome and Its Implication in Renal Dysfunction

Lee

José

2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…In our previous study, we found acute hyperglycemia could lead to obvious renal oxidative stress activation and notable mitochondria damages including mitochondria swelling and irrecognizable mitochondrial crista (2). ROS is mainly produced by mitochondria, and excess ROS accumulation can aggravate mitochondria damages and even cell apoptosis (5). Clearing away damaged mitochondria in time is crucial for cellular homeostasis.…”

Section: Introductionmentioning

confidence: 98%

Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition

et al. 2020

View full text Add to dashboard Cite

AimAcute hyperglycemia is closely related to kidney injury. Oxidative stress activation and notable mitochondria damages were found under acute hyperglycemia treatment in our previous work. In the present study, we explored the dose-effect relationship and the pivotal role of mitophagy in acute hyperglycemia induced tubular injuries.MethodsForty non-diabetic SD rats were randomly divided and treated with different concentrations of hyperglycemia respectively during the 6-h clamp experiment. Renal morphological and functional alterations were detected. Rat renal tubular epithelial cells were treated with different concentrations of glucose for 6 h. Markers and the regulation pathway of mitophagy were analyzed.ResultsSignificant tubular injuries but not glomeruli were observed under both light and electron microscope after acute hyperglycemia treatment, which manifested as enlargement of tubular epithelial cells, disarrangement of epithelial cell labyrinths and swelling of mitochondria. Urinary microalbumin, β2-MG, CysC, NAG, GAL, and NGAL were increased significantly with the increase of blood glucose (P < 0.05). ROS was activated, mitochondrial membrane potential and LC3-II/LC3-I ratio were decreased but P62 and BNIP3L/Nix were increased in hyperglycemia groups (P < 0.05), which were reversed by AMPK activation or mTOR inhibition.ConclusionAcute hyperglycemia causes obvious tubular morphological and functional injuries in a dose-dependent manner. Acute hyperglycemia could inhibit mitophagy through AMPK/mTOR pathway, which would aggravate mitochondria damage and renal tubular impairment.

show abstract

“…The accumulation of damaged mtDNA, fragmented mitochondria, activated apoptosis, loss of MMP, and perturbations in glycolysis and TCA cycle were detected in tubules and PBMCs from the patients. These results indicate that mitochondrial damage may be the hallmark of DKD patients (Jiang et al, 2019).…”

Section: Mitochondrial Haplogroups Associated With Disease In East Asiamentioning

confidence: 88%

Contribution of Mitochondrial DNA Variation to Chronic Disease in East Asian Populations

Sun

Wei

Zheng

et al. 2019

Front. Mol. Biosci.

View full text Add to dashboard Cite

Mitochondria are the main producers of energy in eukaryotic cells. Mitochondrial dysfunction is associated with specific mitochondrial DNA (mtDNA) variations (haplogroups), and these variations can contribute to human disease. East Asian populations show enrichment of many mitochondrial haplogroups, including A, B, D, G, M7, M8, M9, N9, R9, and exhibit half of the known haplogroups of worldwide. In this review, we summarize the current research in the field of mtDNA variation and associated disease in East Asian populations and discuss the physiological and pathological relevance of mitochondrial biology. mtDNA haplogroups are associated with various metabolic disorders ascribed to altered oxidative phosphorylation. The same mitochondrial haplogroup can show either a negative or positive association with different diseases. Mitochondrial dynamics, mitophagy, and mitochondrial oxidative stress, ultimately influence susceptibility to various diseases. In addition, mitochondrial retrograde signaling pathways may have profound effects on nuclear-mitochondrial interactions, affecting cellular morphology, and function. Other complex networks including proteostasis, mitochondrial unfolded protein response and reactive oxygen species signaling may also play pivotal roles in metabolic performance.

show abstract

The Mitochondria-Targeted Metabolic Tubular Injury in Diabetic Kidney Disease

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 50 publications

References 65 publications

Coordinated Contribution of NADPH Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Metabolic Syndrome and Its Implication in Renal Dysfunction

Coordinated Contribution of NADPH Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Metabolic Syndrome and Its Implication in Renal Dysfunction

Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition

Contribution of Mitochondrial DNA Variation to Chronic Disease in East Asian Populations

Contact Info

Product

Resources

About