Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis

Frontiers in Physiology, Год журнала: 2022, Номер 13

Опубликована: Дек. 20, 2022

The mitochondria are essential organelles that generate large amounts of ATP via the electron transport chain (ECT). Mitochondrial dysfunction causes reactive oxygen species accumulation, energy stress, and cell death. Endothelial mitochondrial is an important factor causing abnormal function endothelium, which plays a central role during atherosclerosis development. Atherosclerosis-related risk factors, including high glucose levels, hypertension, ischemia, hypoxia, diabetes, promote in endothelial cells. This review summarizes physiological pathophysiological roles atherosclerosis.

Язык: Английский

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Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling

Acta Neuropathologica Communications, Год журнала: 2021, Номер 9(1)

Опубликована: Июль 7, 2021

Abstract The cellular and molecular mechanisms that drive neurodegeneration remain poorly defined. Recent clinical trial failures, difficult diagnosis, uncertain etiology, lack of curative therapies prompted us to re-examine other hypotheses neurodegenerative pathogenesis. reports establish mitochondrial calcium dysregulation occur early in many diseases (NDDs), including Alzheimer's disease, Parkinson’s Huntington's others. However, causal evidence metabolic contributions pathogenesis remains insufficient. Here we summarize the data supporting hypothesis dysfunction result from diverse etiologies neuropathology. We provide a current comprehensive review literature interpret defective metabolism is upstream primary protein aggregation dogmatic NDDs. Finally, identify gaps knowledge propose therapeutic modulation m Ca 2+ exchange function alleviate impairments treat

Язык: Английский

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PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles

Journal of Nanobiotechnology, Год журнала: 2022, Номер 20(1)

Опубликована: Март 19, 2022

Abstract Copper oxide nanoparticles (CuONPs) are widely used metal NPs owing to their excellent physical–chemical properties. Circulation translocation of CuONPs after inhalation leads vascular endothelial injury. Mitochondria, an important regulatory hub for maintaining cell functions, signaling organelles in responses NPs-induced However, how mitochondrial dynamics (fission and fusion) mitophagy (an autophagy process degrade damaged mitochondria) elaborately orchestrated maintain homeostasis CuONPs-induced injury is still unclear. In this study, we demonstrated that exposure disturbed through oxidative stress-dependent manner cells, as evidenced by the increase fission accumulation fragmented mitochondria. Inhibition with Mdivi-1 aggravated mtROS production death. Furthermore, found led activation PINK1-mediated mitophagy, pharmacological inhibition wortmannin, chloroquine or genetical siRNA-mediated knockdown PINK1 profoundly repressed suggesting protective role toxicity. Intriguingly, identified TAX1BP1 was primary receptor link ubiquitinated mitochondria autophagosomes, since elevated production, decreased clearance cells More importantly, verified urolithin A, a activator, promoted removal induced both vitro vivo. Overall, our findings indicated modulating may be therapeutic strategy pathological caused exposure. Graphical

Язык: Английский

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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

Genes & Diseases, Год журнала: 2023, Номер 11(3), С. 101115 - 101115

Опубликована: Сен. 17, 2023

The liver is an important metabolic and detoxification organ hence demands a large amount of energy, which mainly produced by the mitochondria. Liver tissues patients with alcohol-related or non-alcohol-related diseases contain ultrastructural mitochondrial lesions, DNA damage, disturbed dynamics, compromised ATP production. Overproduction reactive oxygen species induces oxidative damage to proteins DNA, decreases membrane potential, triggers hepatocyte inflammation, promotes programmed cell death, all impair function. Mitochondrial may be potential novel non-invasive biomarker risk progression cirrhosis hepatocellular carcinoma in infected hepatitis B virus. We herein present review mechanisms dysfunction development acute injury chronic diseases, such as carcinoma, viral hepatitis, drug-induced injury, alcoholic disease, non-alcoholic fatty disease. This also discusses mitochondrion-centric therapies for treating diseases.

Язык: Английский

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Mitochondrial Quantity and Quality in Age-Related Sarcopenia

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2052 - 2052

Опубликована: Фев. 8, 2024

Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with complex pathophysiology. Among factors underlying development of sarcopenia are progressive demise motor neurons, transition from fast to slow myosin isoform (type II type I fiber switch), decrease satellite cell number function. Mitochondrial dysfunction has been indicated as key contributor myocyte loss physical performance aging. Several systems have implicated regulation plasticity trophism such fine-tuned between stimulator protein synthesis, mechanistic target rapamycin (mTOR), inhibitor mTOR, AMP-activated kinase (AMPK), that promotes catabolism. Here, we provide an overview molecular mechanisms linking mitochondrial signaling quality homeostasis discuss main pathways elicited by their imbalance during age-related wasting. We also lifestyle interventions (i.e., exercise nutrition) may be exploited preserve function aged muscle. Finally, illustrate emerging possibility rescuing tissue through transplantation.

Язык: Английский

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Mechanism and role of mitophagy in the development of severe infection

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

Опубликована: Фев. 19, 2024

Abstract Mitochondria produce adenosine triphosphate and potentially contribute to proinflammatory responses cell death. Mitophagy, as a conservative phenomenon, scavenges waste mitochondria their components in the cell. Recent studies suggest that severe infections develop alongside mitochondrial dysfunction mitophagy abnormalities. Restoring protects against excessive inflammation multiple organ failure sepsis. Here, we review normal process, its interaction with invading microorganisms immune system, summarize mechanism of during infection. We highlight critical role preventing

Язык: Английский

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Restoring Mitochondrial Function and Muscle Satellite Cell Signaling: Remedies against Age-Related Sarcopenia

Biomolecules, Год журнала: 2024, Номер 14(4), С. 415 - 415

Опубликована: Март 28, 2024

Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular changes fibers in sarcopenia, mitochondria their quality control pathways play relevant roles. Mononucleated stem cells/satellite cells (MSCs) have been attributed critical role repair after an injury. The involvement supporting MSC-directed is unclear. There evidence reduction mitochondrial biogenesis blunts repair, thus indicating delivery functional to injured muscles can be harnessed limit fibrosis enhance restoration function. Injection autologous respiration-competent from uninjured sites damaged tissue shown reduce infarct size cell survival preclinical models ischemia-reperfusion. Furthermore, incorporation donor into MSCs enhances lung cardiac repair. This strategy also tested for regeneration purposes traumatic injuries. Indeed, systemic promotes restores mass function while reducing during recovery In this review, we discuss contribution altered MSC sarcopenia illustrate prospect harnessing as therapeutic against age-related sarcopenia.

Язык: Английский

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Mitochondrial homeostasis: shaping health and disease

Current Medicine, Год журнала: 2024, Номер 3(1)

Опубликована: Апрель 15, 2024

Abstract Mitochondria serve as the primary site for metabolizing three major nutrients, underscoring their pivotal role in cellular energy metabolism and regulation of signaling pathways. Mitochondrial homeostatic imbalance is a key pathological cause development many diseases. Hence, preserving mitochondrial homeostasis vital normal growth cells organisms. Living organisms have evolved intricate regulatory mechanisms to ensure homeostasis. This review focuses on recent advancements comprehending responsible maintaining addresses current challenges this field. We also provide an overview functions mitochondria both physiological conditions. Emphasizing potential therapeutic implications, we discuss strategies homeostasis, recognizing its significance mitigating various health Graphical

Язык: Английский

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Phenylsulfate-induced oxidative stress and mitochondrial dysfunction in podocytes are ameliorated by Astragaloside IV activation of the SIRT1/PGC1α /Nrf1 signaling pathway

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117008 - 117008

Опубликована: Июнь 19, 2024

Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopy，flow cytometry, fluorescence staining, Western blotting other methods. was administered to db/db mice for in vivo experimentation. Our findings indicated that treatment significantly reduced diabetes-associated markers, proteinuria, kidney damage. It also diminished ROS levels kidney, enhanced expression of endogenous antioxidant enzymes, improved health. Phenyl sulfate (PS), a protein-bound uremic solute enteric origin, has been closely linked with DN represents promising avenue further research. vitro, PS exposure induced OS podocytes, increasing while decreasing enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, Glutathione Peroxidase). inhibitors (N-acetyl-L-cysteine, NAC) as positive control group can reduce restore enzymes protein levels. Additionally, markers associated biosynthesis function (SIRT1, PGC1α, Nrf1, TFAM). These adverse effects were partially reversed treatment. However, co-treatment SIRT1 inhibitor EX527 failed these indicators. Overall, our study demonstrates effectively attenuates mitigates PS-induced via SIRT1/PGC1α/Nrf1 pathway.

Язык: Английский

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FUNDC1: A Promising Mitophagy Regulator at the Mitochondria-Associated Membrane for Cardiovascular Diseases

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

Опубликована: Дек. 16, 2021

Mitochondrial autophagy (or mitophagy) regulates the mitochondrial network and function to contribute multiple cellular processes. The protective effect of homeostatic mitophagy in cardiovascular diseases (CVDs) has attracted increasing attention. FUN14 domain containing 1 (FUNDC1), an identified receptor, plays essential role CVDs. Different expression levels FUNDC1 its phosphorylated state at different sites alleviate or exacerbate hypoxia ischemia/reperfusion injury, cardiac hypertrophy, metabolic damage through promotion inhibition mitophagy. In addition, can be enriched contact between mitochondria endoplasmic reticulum (ER), determining formation mitochondria-associated membranes (MAMs) that regulate calcium (Ca2+) homeostasis dynamics prevent heart dysfunction. Moreover, also been involved inflammatory such as septic cardiomyopathy. this review, we collect summarize evidence on roles exclusively various CVDs, describing interactions with organelles, involvement processes, associated signaling pathways. may become a promising therapeutic target for prevention management

Язык: Английский

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