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

Theranostics, Год журнала: 2020, Номер 11(4), С. 1845 - 1863

Опубликована: Дек. 16, 2020

Aims: Ischemia-reperfusion injury (IRI)-induced acute kidney (IRI-AKI) is characterized by elevated levels of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation, but the potential link among these features remains unclear. In this study, we aimed to investigate specific role ROS (mtROS) in initiating DNA (mtDNA) damage inflammation during IRI-AKI. Methods: The changes renal function, IRI-AKI mice with or without mtROS inhibition were analyzed vivo. impact on TFAM (mitochondrial transcription factor A), Lon protease, mtDNA, respiration, cytokine release was tubular cells vitro. effects knockdown also Finally, mtDNA nucleoids measured samples from patients. Results: Decreasing attenuated damage, mice. reversed decrease copy number that occurs HK2 under oxidative stress. reduced abundance suppressing its promoting Lon-mediated degradation. Silencing abolished Mito-Tempo (MT)-induced rescue function Loss found kidneys AKI Conclusion: can promote TFAM-mediated maintenance, resulting decreased energy metabolism increased release. defects may be a promising target for repair after

Язык: Английский

---

Mitochondria ROS and mitophagy in acute kidney injury

Autophagy, Год журнала: 2022, Номер 19(2), С. 401 - 414

Опубликована: Июнь 9, 2022

Mitophagy is an essential mitochondrial quality control mechanism that eliminates damaged mitochondria and the production of reactive oxygen species (ROS). The relationship between oxidative stress, ROS mitophagy are intimately interwoven, these processes all involved in various pathological conditions acute kidney injury (AKI). elimination through mammals a complicated process which involves several pathways. Furthermore, interplay different types cell death, such as apoptosis, pyroptosis ferroptosis unclear. Here we will review recent advances our understanding mitophagy, pathways, relevance pathogenesis AKI.Abbreviations: AKI: injury; AMBRA1: autophagy beclin 1 regulator 1; ATP: adenosine triphosphate; BAK1: BCL2 antagonist/killer BAX: associated X, apoptosis regulator; BCL2: BECN1: BH3: homology domain 3; BNIP3: interacting protein BNIP3L/NIX: 3 like; CASP1: caspase CAT: catalase; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CI-AKI: contrast-induced CISD1: CDGSH iron sulfur CL: cardiolipin; CNP: 2',3'-cyclic nucleotide 3'-phosphodiesterase; DNM1L/DRP1: dynamin E3: enzyme ETC: electron transport chain; FA: folic acid; FUNDC1: FUN14 containing G3P: glycerol-3-phosphate; G6PD: glucose-6-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GSK3B: glycogen synthase kinase beta; GSR: glutathione-disulfide reductase; HIF1A: hypoxia inducible factor subunit alpha; HUWE1: HECT, UBA WWE IL1B: interleukin IMM: inner membrane; IPC: ischemic preconditioning; IRI: ischemia-reperfusion LIR: LC3-interacting region; LPS: lipopolysaccharide; MA: malate-aspartate; MPT: permeability transition; MUL1: E3 ubiquitin ligase mtROS: ROS; NLR: NOD-like receptor; NLRP3: NLR family pyrin NOX: NADPH oxidase; OGD-R: oxygen-glucose deprivation-reperfusion; OMM: outer OPA1: OPA1 like GTPase; OXPHOS: phosphorylation; PARL: presenilin rhomboid PINK1: PTEN induced PLSCR3: phospholipid scramblase PMP: peptidase, processing; PRDX: peroxiredoxin; PRKN: parkin RBR ligase; RPTC: rat proximal tubular cells; ROS: species; SLC7A11/xCT: solute carrier 7 member 11; SOD: superoxide dismutase; SOR: SQSTM1/p62: sequestosome TCA: tricarboxylic TIMM: translocase TOMM: TXN: thioredoxin; VDAC: voltage dependent anion channel; VCP: valosin protein.

Язык: Английский

---

Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress

Frontiers in Physiology, Год журнала: 2021, Номер 12

Опубликована: Апрель 23, 2021

Mitochondria are known to generate approximately 90% of cellular reactive oxygen species (ROS). The imbalance between mitochondrial (mtROS) production and removal due overproduction ROS and/or decreased antioxidants defense activity results in oxidative stress (OS), which leads damage that affects several components such as lipids, DNA, proteins. Since the kidney is a highly energetic organ, it more vulnerable caused by OS thus its contribution development progression chronic disease (CKD). This article aims review mtROS CKD function deterioration.

Язык: Английский

---

Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(5)

Опубликована: Янв. 19, 2021

Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present persistent inflammatory profibrotic response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in fibrosis contributes to its pathogenesis. To determine whether gain function FAO (FAO-GOF) could protect from fibrosis, we generated conditional transgenic mouse model with overexpression fatty shuttling enzyme carnitine palmitoyl-transferase 1A (CPT1A) TECs. Cpt1a-knockin (CPT1A-KI) mice subjected 3 models (unilateral ureteral obstruction, folic nephropathy [FAN], adenine-induced nephrotoxicity) exhibited decreased expression fibrotic markers, blunted proinflammatory response, cell damage macrophage influx. Protection was also observed when Cpt1a induced after FAN. FAO-GOF restored oxidative metabolism mitochondrial number enhanced bioenergetics, increasing palmitate ATP levels, changes that were recapitulated TECs exposed stimuli. Studies patients showed CPT1 levels increased accumulation short- middle-chain acylcarnitines, reflecting impaired human CKD. We propose strategies based on may constitute powerful alternatives combat inherent

Язык: Английский

---

Mitochondrial dysfunction and the AKI-to-CKD transition

AJP Renal Physiology, Год журнала: 2020, Номер 319(6), С. F1105 - F1116

Опубликована: Окт. 19, 2020

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic disease (CKD). Even milder AKI adverse consequences could progress to renal fibrosis, which is ultimate common pathway various terminal diseases. Thus, it urgent develop a strategy hinder transition from CKD. Some mechanisms AKI-to-CKD have revealed, such nephron loss, cell cycle arrest, persistent inflammation, endothelial with vascular rarefaction, epigenetic changes. Previous studies elucidated pivotal role mitochondria in acute injuries demonstrated that fitness this organelle major determinant both pathogenesis recovery organ function. Recent research suggested damage mitochondrial function early crucial leading tubular insufficiency. Dysregulation homeostasis, alterations bioenergetics, stress cross talk contribute transition. In review, we focus on pathophysiology after progression CKD, confirming targeting represents potentially effective therapeutic

Язык: Английский

---

The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(20), С. 11253 - 11253

Опубликована: Окт. 19, 2021

Mitochondria are heterogeneous and highly dynamic organelles, playing critical roles in adenosine triphosphate (ATP) synthesis, metabolic modulation, reactive oxygen species (ROS) generation, cell differentiation death. Mitochondrial dysfunction has been recognized as a contributor many diseases. The kidney is an organ enriched mitochondria with high energy demand the human body. Recent studies have focusing on how mitochondrial contributes to pathogenesis of different forms diseases, including acute injury (AKI) chronic disease (CKD). AKI linked increased risk developing CKD. CKD broad clinical syndrome substantial impact morbidity mortality, encompassing various etiologies representing important challenges for global public health. Renal disorders common feature diverse CKD, which result from defects structure, dynamics, biogenesis well crosstalk other organelles. Persistent dysregulation homeostasis affects cellular pathways, leading increase renal microvascular loss, oxidative stress, apoptosis, eventually failure. It understand molecular events that govern functions pathophysiology should facilitate development novel therapeutic strategies. This review provides overview insights specific pathogenic mechanisms progression AKI, transition. We also discuss possible beneficial effects mitochondrial-targeted agents treatment dysfunction-mediated may translate into options ameliorate delay these

Язык: Английский

---

Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming

Metabolism, Год журнала: 2022, Номер 131, С. 155194 - 155194

Опубликована: Март 26, 2022

Язык: Английский

---

Oxidative stress and the role of redox signalling in chronic kidney disease

Nature Reviews Nephrology, Год журнала: 2023, Номер 20(2), С. 101 - 119

Опубликована: Окт. 19, 2023

Язык: Английский

---

Mitochondrial metabolism and targeted treatment strategies in ischemic-induced acute kidney injury

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 10, 2024

Ischemia-reperfusion injury (IRI) is a common cause of acute kidney (AKI). The susceptible to IRI under several clinical conditions, including hypotension, sepsis, and surgical procedures, such as partial nephrectomy transplantation. Extensive research has been conducted on the mechanism intervention strategies renal in past decades; however, complex pathophysiology IRI-induced AKI (IRI-AKI) not fully understood, there remains lack effective treatments for AKI. Renal involves processes, reactive oxygen species (ROS) production, inflammation, apoptosis. Mitochondria, centers energy metabolism, are increasingly recognized substantial contributors early phases IRI. Multiple mitochondrial lesions have observed tubular epithelial cells (TECs) IRI-AKI mice, damaged or dysfunctional mitochondria toxic because they produce ROS release cell death factors, resulting TEC In this review, we summarize recent advances pathology ischemic highlight promising therapeutic approaches targeting dysfunction prevent treat human

Язык: Английский

---

Inhibition of Drp1- Fis1 interaction alleviates aberrant mitochondrial fragmentation and acute kidney injury

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Март 4, 2024

Acute kidney injury (AKI) is a common clinical disorder with complex etiology and poor prognosis, currently lacks specific effective treatment options. Mitochondrial dynamics dysfunction prominent feature in AKI, modulation of mitochondrial morphology may serve as potential therapeutic approach for AKI.

Язык: Английский

---