Mitochondrial dysfunction in the pathophysiology of renal diseases

2014 ◽  
Vol 306 (4) ◽  
pp. F367-F378 ◽  
Author(s):  
Ruochen Che ◽  
Yanggang Yuan ◽  
Songming Huang ◽  
Aihua Zhang
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Nuclear Dna ◽  
Kidney Diseases ◽  
Mitochondrial Dynamics ◽  
Critical Role ◽  
Kidney Injury ◽  
High Energy ◽  
Renal Diseases ◽  
Glomerular Diseases

Mitochondrial dysfunction has gained recognition as a contributing factor in many diseases. The kidney is a kind of organ with high energy demand, rich in mitochondria. As such, mitochondrial dysfunction in the kidney plays a critical role in the pathogenesis of kidney diseases. Despite the recognized importance mitochondria play in the pathogenesis of the diseases, there is limited understanding of various aspects of mitochondrial biology. This review examines the physiology and pathophysiology of mitochondria. It begins by discussing mitochondrial structure, mitochondrial DNA, mitochondrial reactive oxygen species production, mitochondrial dynamics, and mitophagy, before turning to inherited mitochondrial cytopathies in kidneys (inherited or sporadic mitochondrial DNA or nuclear DNA mutations in genes that affect mitochondrial function). Glomerular diseases, tubular defects, and other renal diseases are then discussed. Next, acquired mitochondrial dysfunction in kidney diseases is discussed, emphasizing the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease and acute kidney injury, as their prevalence is increasing. Finally, it summarizes the possible beneficial effects of mitochondrial-targeted therapeutic agents for treatment of mitochondrial dysfunction-mediated kidney injury-genetic therapies, antioxidants, thiazolidinediones, sirtuins, and resveratrol-as mitochondrial-based drugs may offer potential treatments for renal diseases.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Renal involvement in pediatric patients with COVID-19: an up-to-date

2021 ◽  
Vol 17 ◽  
Author(s):  
Yuri Márcio Campos ◽  
André Luís Vieira Drumond ◽  
Mariane de Matos Gamonal ◽  
Milena Pereira Parreira ◽  
Ana Cristina Simões e Silva
Keyword(s):  
At Risk ◽  
Acute Kidney Injury ◽  
Pediatric Patients ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Glomerular Diseases ◽  
Report Data

Background: In pediatric patients, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has been mostly associated with mild symptoms. However, as in adults, renal involvement has been reported in children and adolescents with Coronavirus Disease 2019 (COVID-19). Objective: This review aimed to report data about renal involvement in pediatric COVID-9. The focuses were on the pathophysiology of acute kidney injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated (PIMS-TS) with SARS-CoV-2 and the possible impact of SARS-CoV-2 infection upon kidney function, as well as data concerning patients with previous kidney diseases, including Nephrotic Syndrome and Chronic Renal Disease. The implications for COVID-19 outcome in pediatric patients were also discussed. Methods: This integrative review searched for articles on renal involvement in pediatric COVID-19 patients. The databases evaluated were PubMed and Scopus. Results: The emergence of PIMS-TS with SARS-CoV-2 has shown that pediatric patients are at risk of severe COVID-19, with multi-organ involvement and dysfunction. In addition to intense inflammation, several systems are affected in this syndrome, collectively creating a combination of factors that results in acute kidney injury. Several studies have proposed that kidney cells, including the podocytes, might be at risk of direct infection by SARS-CoV-2, as high levels of ACE2, the virus receptor, are expressed on the membrane of such cells. Some cases of glomerular diseases triggered by SARS-CoV-2 infection and relapses of previous renal diseases have been reported. Conclusion: Further studies are necessary to establish risk factors for renal involvement in pediatric COVID-19 and to predict disease outcome.

scholarly journals Renal Diseases Associated with Hematologic Malignancies and Thymoma in the Absence of Renal Monoclonal Immunoglobulin Deposits

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 710
Author(s):  
Antoine Morel ◽  
Marie-Sophie Meuleman ◽  
Anissa Moktefi ◽  
Vincent Audard
Keyword(s):  
Kidney Diseases ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Myeloproliferative Disorders ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Renal Diseases ◽  
Diagnostic Strategy ◽  
Monoclonal Immunoglobulin ◽  
Glomerular Diseases

In addition to kidney diseases characterized by the precipitation and deposition of overproduced monoclonal immunoglobulin and kidney damage due to chemotherapy agents, a broad spectrum of renal lesions may be found in patients with hematologic malignancies. Glomerular diseases, in the form of paraneoplastic glomerulopathies and acute kidney injury with various degrees of proteinuria due to specific lymphomatous interstitial and/or glomerular infiltration, are two major renal complications observed in the lymphoid disorder setting. However, other hematologic neoplasms, including chronic lymphocytic leukemia, thymoma, myeloproliferative disorders, Castleman disease and hemophagocytic syndrome, have also been associated with the development of kidney lesions. These renal disorders require prompt recognition by the clinician, due to the need to implement specific treatment, depending on the chemotherapy regimen, to decrease the risk of subsequent chronic kidney disease. In the context of renal disease related to hematologic malignancies, renal biopsy remains crucial for accurate pathological diagnosis, with the aim of optimizing medical care for these patients. In this review, we provide an update on the epidemiology, clinical presentation, pathophysiological processes and diagnostic strategy for kidney diseases associated with hematologic malignancies outside the spectrum of monoclonal gammopathy of renal significance.

scholarly journals Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders

2021 ◽  
Author(s):  
George B. Stefano ◽  
Richard M. Kream
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Specific ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Mitochondrial Dna Heteroplasmy

AbstractMitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

Abstract 206: Accumulation of Mitochondrial DNA Mutations Impairs Survival, Proliferation, and Differentiation of Cardiac Progenitor Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Amabel M Orogo ◽  
Dieter A Kubli ◽  
Anne N Murphy ◽  
Åsa B Gustafsson
Keyword(s):  
Mitochondrial Dna ◽  
Progenitor Cells ◽  
Mitochondrial Biogenesis ◽  
Nuclear Dna ◽  
Critical Role ◽  
Chemotherapeutic Agents ◽  
Cardiac Progenitor Cells ◽  
Mtdna Mutations ◽  
Differentiation Medium ◽  
Proliferation And Differentiation

Activation and participation of cardiac progenitor cells (CPCs) in regeneration are critical for effective repair in the wake of pathologic injury. Stem cell activation and commitment involve increased energy demand and mitochondrial biogenesis. To date, little attention has been paid to the importance of mitochondria in CPC survival, proliferation and differentiation. CPC function is reduced with age but the underlying mechanism is still unclear. Mitochondrial DNA (mtDNA) is more susceptible to oxidative attacks than nuclear DNA due to its proximity to the mitochondrial respiratory chain and lack of protective histone-like proteins. With age, mtDNA accumulates mutations that can impair mitochondrial respiration and increase ROS production. In this study, we examined the effects of accumulating mtDNA mutations on CPC proliferation and survival. We have found that incubation of uncommitted c-kit+ CPCs in differentiation medium increased mitochondrial mass and expansion of the mitochondrial network, which correlated with increased cell size and expression of cardiac lineage commitment markers. Differentiation activated mitochondrial biogenesis, increased mtDNA copy number, and enhanced oxidative capacity and cellular ATP levels in CPCs. To investigate the effect of mtDNA mutations and aging on CPC survival and function, we utilized a mouse model in which a mutation in the mtDNA polymerase γ (POLG m/m ) leads to accumulation of mtDNA mutations, mitochondrial dysfunction, and accelerated aging. Isolated CPCs from hearts of 2-month old POLG m/m mice had reduced proliferation and were more susceptible to oxidative stress and chemotherapeutic agents compared to WT CPCs. The majority of POLG m/m CPCs contained fragmented mitochondria as shown by immunostaining. Incubation in differentiation medium resulted in fewer GATA-4 positive POLG m/m CPCs compared to WT CPCs. The reduced differentiation in these POLG m/m CPCs correlated with reduced PGC-1α expression and OXPHOS protein levels, suggesting that mitochondrial biogenesis is impaired. These data demonstrate that mitochondria play a critical role in CPC function, and accumulation of mtDNA mutations impairs CPC function and reduces their repair potential.

Renal medicine

2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Renal Stones ◽  
Renal Diseases ◽  
Acute Glomerulonephritis ◽  
Glomerular Diseases ◽  
Stage Renal Disease ◽  
End Stage

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases

scholarly journals Altered Mitochondrial Dynamics in Motor Neuron Disease: An Emerging Perspective

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1065 ◽  
Author(s):  
Manohar Kodavati ◽  
Haibo Wang ◽  
Muralidhar L. Hegde
Keyword(s):  
Mitochondrial Dna ◽  
Dna Binding ◽  
Motor Neuron ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Motor Neuron Diseases ◽  
Potential Implication ◽  
Fused In Sarcoma ◽  
Apoptotic Pathways

Mitochondria plays privotal role in diverse pathways that regulate cellular function and survival, and have emerged as a prime focus in aging and age-associated motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Accumulating evidence suggests that many amyloidogenic proteins, including MND-associated RNA/DNA-binding proteins fused in sarcoma (FUS) and TAR DNA binding protein (TDP)-43, are strongly linked to mitochondrial dysfunction. Animal model and patient studies have highlighted changes in mitochondrial structure, plasticity, replication/copy number, mitochondrial DNA instability, and altered membrane potential in several subsets of MNDs, and these observations are consistent with the evidence of increased excitotoxicity, induction of reactive oxygen species, and activation of intrinsic apoptotic pathways. Studies in MND rodent models also indicate that mitochondrial abnormalities begin prior to the clinical and pathological onset of the disease, suggesting a causal role of mitochondrial dysfunction. Our recent studies, which demonstrated the involvement of specific defects in DNA break-ligation mediated by DNA ligase 3 (LIG3) in FUS-associated ALS, raised a key question of its potential implication in mitochondrial DNA transactions because LIG3 is essential for both mitochondrial DNA replication and repair. This question, as well as how wild-type and mutant MND-associated factors affect mitochondria, remain to be elucidated. These new investigation avenues into the mechanistic role of mitochondrial dysfunction in MNDs are critical to identify therapeutic targets to alleviate mitochondrial toxicity and its consequences. In this article, we critically review recent advances in our understanding of mitochondrial dysfunction in diverse subgroups of MNDs and discuss challenges and future directions.

scholarly journals Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

2021 ◽  
Vol 11 (8) ◽  
pp. 820
Author(s):  
Mengyuan Ge ◽  
Sandra Merscher ◽  
Alessia Fornoni
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Recent Progress ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Glomerular Diseases ◽  
Intracellular Lipids ◽  
Lipid Modifying Agents ◽  
Made In

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

scholarly journals iTRAQ-based comparative proteomics analysis reveals specific urinary biomarkers for various kidney diseases

2019 ◽  
Author(s):  
Juan Jin ◽  
Jianguang Gong ◽  
Li Zhao ◽  
Yiwen Li ◽  
Qiang He
Keyword(s):  
Biomarker Discovery ◽  
Bioinformatics Analysis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Urinary Proteins ◽  
Proteomics Analysis ◽  
Kegg Pathway Analysis ◽  
Go Enrichment ◽  
Differentially Abundant Proteins

Abstract Background Urinary proteomics has been extensively applied to investigate renal diseases including acute kidney injury (AKI), chronic kidney disease (CKD), IgA nephropathy (IgAN) and diabetic CKD. However, differential urinary proteome studies have not been reported for multiple diseases. The present study was aimed to explore early clinical diagnosis biomarkers for patients with AKI, AKI+CKD, diabetic CKD, non-diabetic CKD with IgAN and non-diabetic CKD without IgAN. Methods Differentially expressed proteins (DEPs) were screened by iTRAQ labeling and 2-D LC-MS/MS. Bioinformatics analysis was performed by subsequent GO enrichment and KEGG pathway analysis. DEPs were authenticated by ELISA assay. Results 156, 156, 286, 187 and 184 differentially abundant proteins were identified in patients with AKI, AKI+CKD, diabetic CKD, and non-diabetic CKD with or without IgAN. Comparative analysis indicated that 34, 35 and 17 unique DEPs were found in AKI, AKI+CKD and CKD samples, respectively. 91 and 14 specific DEPs were screened out in diabetic CKD and non-diabetic CKD. In comparison with Non-diabetic CKD with IgAN (38 DEPs), 47 unique urinary proteins were found in Non-diabetic CKD without IgAN. Among these DEPs, urinary SAA1 and HGFAC were only unregulated in AKI and Non-diabetic CKD without IgAN implying that they might be employed as the potential indicators of the two diseases. C5, APOC1 and Reg3A upregulation was not exclusively expressed in each disease which suggested that they could not be used for biomarker to distinguish one disease from the other. Conclusion Collectively, this research contributes to the urinary biomarker discovery from multiple renal diseases.

scholarly journals Mitochondrial Dysfunction in Parkinson’s Disease: Focus on Mitochondrial DNA

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 591
Author(s):  
Olga Buneeva ◽  
Valerii Fedchenko ◽  
Arthur Kopylov ◽  
Alexei Medvedev
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Nuclear Dna ◽  
Good Evidence ◽  
Inner Mitochondrial Membrane ◽  
Mtdna Mutations ◽  
Increased Risk ◽  
Mtdna Replication

Mitochondria, the energy stations of the cell, are the only extranuclear organelles, containing their own (mitochondrial) DNA (mtDNA) and the protein synthesizing machinery. The location of mtDNA in close proximity to the oxidative phosphorylation system of the inner mitochondrial membrane, the main source of reactive oxygen species (ROS), is an important factor responsible for its much higher mutation rate than nuclear DNA. Being more vulnerable to damage than nuclear DNA, mtDNA accumulates mutations, crucial for the development of mitochondrial dysfunction playing a key role in the pathogenesis of various diseases. Good evidence exists that some mtDNA mutations are associated with increased risk of Parkinson’s disease (PD), the movement disorder resulted from the degenerative loss of dopaminergic neurons of substantia nigra. Although their direct impact on mitochondrial function/dysfunction needs further investigation, results of various studies performed using cells isolated from PD patients or their mitochondria (cybrids) suggest their functional importance. Studies involving mtDNA mutator mice also demonstrated the importance of mtDNA deletions, which could also originate from abnormalities induced by mutations in nuclear encoded proteins needed for mtDNA replication (e.g., polymerase γ). However, proteomic studies revealed only a few mitochondrial proteins encoded by mtDNA which were downregulated in various PD models. This suggests nuclear suppression of the mitochondrial defects, which obviously involve cross-talk between nuclear and mitochondrial genomes for maintenance of mitochondrial functioning.

Sign in / Sign up

Export Citation Format

Share Document