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 Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration

Antioxidants, Год журнала: 2020, Номер 9(8), С. 647 - 647

Опубликована: Июль 22, 2020

Oxidative stress develops as a response to injury and reflects breach in the cell’s antioxidant capacity. Therefore, fine-tuning of reactive oxygen species (ROS) generation is crucial for preserving homeostasis. Mitochondria are major source an immediate target ROS. Under different stimuli, including oxidative impaired quality control, mitochondrial constituents (e.g., DNA, mtDNA) displaced toward intra- or extracellular compartments. However, mechanisms responsible mtDNA unloading remain largely unclear. While shuttling freely within cell, can be delivered into compartment via either extrusion entire nucleoids release vesicles. Once discarded, may act damage-associated molecular pattern (DAMP) trigger innate immune inflammatory by binding danger-signal receptors. Neuroinflammation associated with large array neurological disorders which DAMPs could represent common thread supporting disease progression. The exploration non-canonical pathways involved control neurodegeneration unveil novel targets development therapeutic agents. Here, we discuss these processes setting two neurodegenerative diseases (Alzheimer’s Parkinson’s disease) Down syndrome, most frequent progeroid syndrome.

Язык: Английский

---

Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?

Journal of Biomedical Science, Год журнала: 2022, Номер 29(1)

Опубликована: Сен. 26, 2022

The major concept of "oxidative stress" is an excess elevated level reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption oxygen. precise harmonization oxidative stresses between mitochondria other organelles in the cell absolutely vital to survival. Under stress, ROS produced mediator for tumorigenesis different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, immunoescape allow cancer cells adapt rigorous environment. Accordingly, dynamic balance not only orchestrate complex signaling events but also affect components tumor microenvironment (TME). Immune cells, M2 macrophages, dendritic T immunosuppressive TME ROS-induced inflammation. Based on this notion, numerous strategies mitigate tumors have been tested prevention or therapies; however, these manipulations devised sources mechanisms without established effectiveness. Herein, we integrate current progress regarding impact mitochondrial TME, immune discuss combination emerging ROS-modulating with immunotherapies achieve antitumor effects.

Язык: Английский

---

Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD

Hepatology, Год журнала: 2022, Номер 76(5), С. 1452 - 1465

Опубликована: Янв. 9, 2022

NAFLD and its more-advanced form, steatohepatitis (NASH), is associated with obesity an independent risk factor for cardiovascular, liver-related, all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) turnover in NASH are scant.To investigate this relationship, liver biopsies were obtained from patients undergoing bariatric surgery clustered into four groups based on histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline-NASH lobular inflammation or hepatocellular ballooning); Definite-NASH (D-NASH; steatosis, inflammation, ballooning). Hepatic complete FAO to CO2 the rate-limiting enzyme β-oxidation (β-hydroxyacyl-CoA dehydrogenase activity) reduced by ~40%-50% D-NASH compared CTRL. This corresponded increased reactive oxygen species production, as well dramatic reductions markers of biogenesis, autophagy, mitophagy, fission, fusion NASH.These findings suggest that compromised intimately linked increasing severity obesity.

Язык: Английский

---

Cell Death and Inflammation: The Role of Mitochondria in Health and Disease

Cells, Год журнала: 2021, Номер 10(3), С. 537 - 537

Опубликована: Март 3, 2021

Mitochondria serve as a hub for multitude of vital cellular processes. To ensure an efficient deployment mitochondrial tasks, organelle homeostasis needs to be preserved. Mitochondrial quality control (MQC) mechanisms (i.e., dynamics, biogenesis, proteostasis, and autophagy) are in place safeguard integrity functionality. Defective MQC has been reported several conditions characterized by chronic low-grade inflammation. In this context, the displacement components, including DNA (mtDNA), into extracellular compartment is possible factor eliciting innate immune response. The presence bacterial-like CpG islands mtDNA makes molecule recognized damaged-associated molecular pattern system. Following cell death-triggering stressors, can released from ignite inflammation via pathways. Crosstalk between autophagy apoptosis emerged pivotal regulation release, cell's fate, repression mtDNA-mediated interferon production, powerful driver immunological death, also regulated autophagy-apoptosis crosstalk. Interferon production during may exploited elimination dying cells their conversion elements driving anti-tumor immunity.

Язык: Английский

---

Mitochondria: It is all about energy

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Апрель 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Язык: Английский

---

The Mitochondrial Response to DNA Damage

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Май 12, 2021

Mitochondria are double membrane organelles in eukaryotic cells that provide energy by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They crucial to many aspects of cellular metabolism. contain their own DNA encodes for essential proteins involved the execution normal mitochondrial functions. Compared with nuclear DNA, (mtDNA) is more prone be affected damaging agents, and accumulated damages may cause dysfunction drive pathogenesis a variety human diseases, including neurodegenerative disorders cancer. Therefore, understanding better how mtDNA repaired will facilitate developing therapeutic strategies. In this review, we focus on our current repair system. We also discuss other events promoted excessive inefficient repair, such as fusion, fission, mitophagy, which serve quality control clearing damaged mtDNA.

Язык: Английский

---

Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy

Redox Biology, Год журнала: 2022, Номер 52, С. 102304 - 102304

Опубликована: Апрель 6, 2022

As essential regulators of mitochondrial quality control, dynamics and mitophagy play key roles in maintenance metabolic health cellular homeostasis. Here we show that knockdown the membrane-inserted scaffolding structural protein caveolin-1 (Cav-1) expression tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered morphology, increased matrix mixing, fusion fission well MDA-MB-231 triple negative breast cancer cells. Further, found interaction with fusion/fission machinery Mitofusin 2 (Mfn2) Dynamin related 1 (Drp1) was enhanced by Y14D indicating Y14 phosphorylation prevented Mfn2 Drp1 translocation mitochondria. Moreover, limiting recruitment diminished formation PINK1/Mfn2/Parkin complex required for initiation resulting accumulation damaged mitochondria ROS (mtROS). Thus, these studies indicate phospho-Cav-1 may be an important switch mechanism cell survival which could lead novel strategies complementing therapies.

Язык: Английский

---

Mitochondrial Dysfunction, Oxidative Stress, and Therapeutic Strategies in Diabetes, Obesity, and Cardiovascular Disease

Antioxidants, Год журнала: 2023, Номер 12(3), С. 658 - 658

Опубликована: Март 7, 2023

Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They the site of important biochemical pathways, tricarboxylic acid cycle, parts ureagenesis or haem synthesis. responsible for majority ATP production through OXPHOS. Mitochondrial dysfunction has been associated with metabolic pathologies such as diabetes, obesity, hypertension, neurodegenerative diseases, aging, cancer. In this article, we describe pathophysiological changes in, mitochondrial role of, disorders (diabetes, cardiovascular disease) their correlation oxidative stress. We highlight genetic identified at mtDNA level. Additionally, selected several representative biomarkers stress summarize progress therapeutic strategies.

Язык: Английский

---

Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Май 24, 2023

Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents leading cause mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade pathophysiological events following restoration blood flow reoxygenation, not only directly damages brain tissue, but also enhances series pathological signaling cascades, contributing to inflammation, further aggravate damage tissue. Paradoxically, there are still no effective methods prevent CI/RI, since detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, characterized by mitochondrial oxidative stress, Ca 2+ overload, iron dyshomeostasis, DNA (mtDNA) defects quality control (MQC) disruption, closely relevant process CI/RI. There increasing evidence that dysfunctions play vital roles in regulation programmed cell deaths (PCDs) such as ferroptosis PANoptosis, newly proposed conception unique form innate immune inflammatory death regulated multifaceted PANoptosome complexes. In present review, we highlight how this key event contributes response well modes during Neuroprotective agents targeting may serve promising treatment strategy alleviate serious secondary injuries. A comprehensive insight into dysfunctions-mediated PCDs can help provide strategies guide therapies CI/RI IS.

Язык: Английский

---