scholarly journals The Loss of Mitochondrial Quality Control in Diabetic Kidney Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenni Dai ◽  
Hengcheng Lu ◽  
Yinyin Chen ◽  
Danyi Yang ◽  
Lin Sun ◽  
...  
Keyword(s):  
Quality Control ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Protein Quality ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Protein ◽  
Eukaryotic Cell ◽  
Mitochondrial Quality Control ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.

scholarly journals KCa3.1 Mediates Dysregulation of Mitochondrial Quality Control in Diabetic Kidney Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunling Huang ◽  
Hao Yi ◽  
Ying Shi ◽  
Qinghua Cao ◽  
Yin Shi ◽  
...  
Keyword(s):  
Quality Control ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Mice ◽  
Mitochondrial Quality Control ◽  
Diabetic Kidney ◽  
Hk2 Cells ◽  
Tgf Β1

Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease. Mitochondrial quality control is primarily mediated by mitochondrial turnover and repair through mitochondrial fission/fusion and mitophagy. We have previously shown that blockade of the calcium-activated potassium channel KCa3.1 ameliorates diabetic renal fibrosis. However, the mechanistic link between KCa3.1 and mitochondrial quality control in diabetic kidney disease is not yet known. Transforming growth factor β1 (TGF-β1) plays a central role in diabetic kidney disease. Recent studies indicate an emerging role of TGF-β1 in the regulation of mitochondrial function. However, the molecular mechanism mediating mitochondrial quality control in response to TGF-β1 remains limited. In this study, mitochondrial function was assessed in TGF-β1-exposed renal proximal tubular epithelial cells (HK2 cells) transfected with scrambled siRNA or KCa3.1 siRNA. In vivo, diabetes was induced in KCa3.1+/+ and KCa3.1−/− mice by low-dose streptozotocin (STZ) injection. Mitochondrial fission/fusion-related proteins and mitophagy markers, as well as BCL2 interacting protein 3 (BNIP3) (a mitophagy regulator) were examined in HK2 cells and diabetic mice kidneys. The in vitro results showed that TGF-β1 significantly inhibited mitochondrial ATP production rate and increased mitochondrial ROS (mtROS) production when compared to control, which was normalized by KCa3.1 gene silencing. Increased fission and suppressed fusion were found in both TGF-β1-treated HK2 cells and diabetic mice, which were reversed by KCa3.1 deficiency. Furthermore, our results showed that mitophagy was inhibited in both in vitro and in vivo models of diabetic kidney disease. KCa3.1 deficiency restored abnormal mitophagy by inhibiting BNIP3 expression in TGF-β1-induced HK2 cells as well as in the diabetic mice. Collectively, these results indicate that KCa3.1 mediates the dysregulation of mitochondrial quality control in diabetic kidney disease.

scholarly journals Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

2021 ◽  
Vol 10 (10) ◽  
pp. 2046
Author(s):  
Goren Saenz-Pipaon ◽  
Saioa Echeverria ◽  
Josune Orbe ◽  
Carmen Roncal
Keyword(s):  
Kidney Disease ◽  
Extracellular Vesicles ◽  
Diabetic Kidney Disease ◽  
Current Knowledge ◽  
Developed Countries ◽  
Disease Diagnosis ◽  
Renal Diseases ◽  
Diabetic Kidney ◽  
Glucose Levels ◽  
Stage Renal Disease

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.

scholarly journals The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1525
Author(s):  
Chunling Huang ◽  
Ji Bian ◽  
Qinghua Cao ◽  
Xin-Ming Chen ◽  
Carol A. Pollock
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Mitochondrial Protein ◽  
Physiological Role ◽  
Close Link ◽  
Promising Alternative ◽  
Diabetic Kidney ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

Protein quality control at the mitochondrion

2016 ◽  
Vol 60 (2) ◽  
pp. 213-225 ◽  
Author(s):  
Wolfgang Voos ◽  
Witold Jaworek ◽  
Anne Wilkening ◽  
Michael Bruderek
Keyword(s):  
Quality Control ◽  
Structural Integrity ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control ◽  
Eukaryotic Cell ◽  
Control Mechanisms ◽  
Biochemical Processes ◽  
Unfolded Protein ◽  
Protein Response

Mitochondria are essential constituents of a eukaryotic cell by supplying ATP and contributing to many mayor metabolic processes. As endosymbiotic organelles, they represent a cellular subcompartment exhibiting many autonomous functions, most importantly containing a complete endogenous machinery responsible for protein expression, folding and degradation. This article summarizes the biochemical processes and the enzymatic components that are responsible for maintaining mitochondrial protein homoeostasis. As mitochondria lack a large part of the required genetic information, most proteins are synthesized in the cytosol and imported into the organelle. After reaching their destination, polypeptides must fold and assemble into active proteins. Under pathological conditions, mitochondrial proteins become misfolded or damaged and need to be repaired with the help of molecular chaperones or eventually removed by specific proteases. Failure of these protein quality control mechanisms results in loss of mitochondrial function and structural integrity. Recently, novel mechanisms have been identified that support mitochondrial quality on the organellar level. A mitochondrial unfolded protein response allows the adaptation of chaperone and protease activities. Terminally damaged mitochondria may be removed by a variation of autophagy, termed mitophagy. An understanding of the role of protein quality control in mitochondria is highly relevant for many human pathologies, in particular neurodegenerative diseases.

scholarly journals Mitochondrial dynamics, quality control and miRNA regulation in skeletal muscle: implications for obesity and related metabolic disease

2016 ◽  
Vol 130 (11) ◽  
pp. 843-852 ◽  
Author(s):  
Dennis Dahlmans ◽  
Alexandre Houzelle ◽  
Patrick Schrauwen ◽  
Joris Hoeks
Keyword(s):  
Metabolic Disease ◽  
Skeletal Muscle ◽  
Quality Control ◽  
Dietary Habits ◽  
Protein Quality ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Protein ◽  
Mirna Regulation ◽  
Cellular Energy ◽  
Post Transcriptional Regulation

The western dietary habits and sedentary lifestyle largely contributes to the growing epidemic of obesity. Mitochondria are at the front line of cellular energy homoeostasis and are implicated in the pathophysiology of obesity and obesity-related metabolic disease. In recent years, novel aspects in the regulation of mitochondrial metabolism, such as mitochondrial dynamics, mitochondrial protein quality control and post-transcriptional regulation of genes coding for mitochondrial proteins, have emerged. In this review, we discuss the recent findings concerning the dysregulation of these processes in skeletal muscle in obesogenic conditions.

scholarly journals Mitochondria in Diabetic Kidney Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2945
Author(s):  
Amna Ayesha Ahmad ◽  
Shayna Odeal Draves ◽  
Mariana Rosca
Keyword(s):  
Kidney Disease ◽  
Posttranslational Modifications ◽  
Energy Demand ◽  
Diabetic Kidney Disease ◽  
Mitochondrial Dynamics ◽  
Redox Status ◽  
Substrate Selection ◽  
Tubular Atrophy ◽  
Diabetic Kidney ◽  
The Usa

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in the USA. The pathogenesis of DKD is multifactorial and involves activation of multiple signaling pathways with merging outcomes including thickening of the basement membrane, podocyte loss, mesangial expansion, tubular atrophy, and interstitial inflammation and fibrosis. The glomerulo-tubular balance and tubule-glomerular feedback support an increased glomerular filtration and tubular reabsorption, with the latter relying heavily on ATP and increasing the energy demand. There is evidence that alterations in mitochondrial bioenergetics in kidney cells lead to these pathologic changes and contribute to the progression of DKD towards ESRD. This review will focus on the dialogue between alterations in bioenergetics in glomerular and tubular cells and its role in the development of DKD. Alterations in energy substrate selection, electron transport chain, ATP generation, oxidative stress, redox status, protein posttranslational modifications, mitochondrial dynamics, and quality control will be discussed. Understanding the role of bioenergetics in the progression of diabetic DKD may provide novel therapeutic approaches to delay its progression to ESRD.

scholarly journals Mitochondrial quality control in intervertebral disc degeneration

2021 ◽  
Author(s):  
Yu Song ◽  
Saideng Lu ◽  
Wen Geng ◽  
Xiaobo Feng ◽  
Rongjin Luo ◽  
...  
Keyword(s):  
Quality Control ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Intervertebral Discs ◽  
Mitochondrial Quality Control

AbstractIntervertebral disc degeneration (IDD) is a common and early-onset pathogenesis in the human lifespan that can increase the risk of low back pain. More clarification of the molecular mechanisms associated with the onset and progression of IDD is likely to help establish novel preventive and therapeutic strategies. Recently, mitochondria have been increasingly recognized as participants in regulating glycolytic metabolism, which has historically been regarded as the main metabolic pathway in intervertebral discs due to their avascular properties. Indeed, mitochondrial structural and functional disruption has been observed in degenerated nucleus pulposus (NP) cells and intervertebral discs. Multilevel and well-orchestrated strategies, namely, mitochondrial quality control (MQC), are involved in the maintenance of mitochondrial integrity, mitochondrial proteostasis, the mitochondrial antioxidant system, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Here, we address the key evidence and current knowledge of the role of mitochondrial function in the IDD process and consider how MQC strategies contribute to the protective and detrimental properties of mitochondria in NP cell function. The relevant potential therapeutic treatments targeting MQC for IDD intervention are also summarized. Further clarification of the functional and synergistic mechanisms among MQC mechanisms may provide useful clues for use in developing novel IDD treatments.

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