Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258

Published: June 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Language: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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Visualizing Endoplasmic Reticulum Stress and Autophagy in Alzheimer’s Model Cells by a Peroxynitrite-Responsive AIEgen Fluorescent Probe

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: 16(2), P. 223 - 231

Published: Jan. 7, 2025

Endoplasmic reticulum (ER) stress and autophagy (ER-phagy) occurring in nerve cells are crucial physiological processes closely associated with Alzheimer's disease (AD). Visualizing the two is paramount to advance our understanding of AD pathologies. Among biomarkers identified, peroxynitrite (ONOO-) emerges as a key molecule initiation aggravation ER ER-phagy, highlighting its significance underlying mechanisms processes. In this work, we designed synthesized an innovative ONOO--responsive AIEgen-based fluorescent probe (DHQM) ability monitor ER-phagy model cells. DHQM demonstrated excellent aggregation-induced emission (AIE) properties, endowing it outstanding for washing-free intracellular imaging. Meanwhile, exhibited high sensitivity, remarkable selectivity ONOO-, exceptional ER-targeting ability. The was successfully applied fluorescence imaging ONOO- fluctuations assess status aluminum-induced Our findings revealed that ferroptosis, regulated cell death process, pivotal excessive production, which turn activated exacerbated stress. Furthermore, aluminum-stimulated observed utilizing DHQM, might be inhibiting ferroptosis mitigating aberrant Overall, study not only offers valuable insights into pathological at level but also opens new potential therapeutic avenues targeting these pathways.

Language: Английский

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Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: 15(3), P. 1589 - 1607

Published: Jan. 2, 2025

Iron overload is strongly associated with heart disease. Ferroptosis a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism myocardial injury caused by iron still unclear, and involvement ferroptosis overload-induced not fully understood. In this study, we observed that participated developing I/R-induced cardiomyopathy. Mechanistically, discovered Parkin inhibited cardiomyocytes promoting ubiquitination long-chain acyl-CoA synthetase 4 (ACSL4), crucial protein involved ferroptosis-related lipid metabolism pathways. Additionally, identified p53 as transcription factor transcriptionally suppressed expression iron-overloaded cardiomyocytes, thereby regulating ferroptosis. animal studies, cardiac-specific knockout mice (Myh6-CreER T2 /Parkin fl/fl ) fed high-iron diet presented more severe damage, high levels exacerbated I/R inhibitor Fer-1 significantly Moreover, effectively protected against impaired mitochondrial function prevented peroxidation. These findings unveil novel regulatory pathway involving p53-Parkin-ACSL4 disease inhibiting

Language: Английский

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The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119555 - 119555

Published: Feb. 1, 2025

Language: Английский

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Coordinating BNIP3/NIX-mediated mitophagy in space and time

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(5), P. 1969 - 1979

Published: Oct. 8, 2024

Mitochondria maintain organellar homeostasis through multiple quality control pathways, including the clearance of defective or unwanted mitochondria by selective autophagy. This removal mitochondria, mitophagy, is controlled in large part outer mitochondrial membrane mitophagy receptors BNIP3 and NIX. While it has long been appreciated that NIX mediate controlling recruitment autophagic machinery to surface, requirement for carefully spatiotemporal regulation receptor-mediated only recently come light. Several new factors regulate BNIP3/NIX-mediated pathway have emerged, various loss-of-function cell animal models revealed dire consequences their dysregulation. In this mini-review, we discuss insights into mechanisms roles highlight questions emerged from identification these regulators.

Language: Английский

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Mitophagy and Ferroptosis in Sepsis-Induced ALI/ARDS: Molecular Mechanisms, Interactions and Therapeutic Prospects of Medicinal Plants

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 7819 - 7835

Published: Oct. 1, 2024

Sepsis is a common critical illness characterized by high mortality rates and significant disease burden. In the context of sepsis-induced organ dysfunction, lungs are among initial organs affected, which may progress to acute lung injury (ALI) respiratory distress syndrome (ARDS). Recent studies have highlighted crucial roles mitophagy ferroptosis in development progression ALI/ARDS. Identifying key convergence points these processes provide valuable insights for treatment this condition. recent years, certain herbs their bioactive compounds demonstrated unique benefits managing ALI/ARDS modulating or ferroptosis. This review summary mechanisms ferroptosis, explores interactions, emphasizes regulatory Additionally, it offers novel perspective on strategies summarizing various relevant

Language: Английский

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Cell life-or-death events in osteoporosis: All roads lead to mitochondrial dynamics

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107383 - 107383

Published: Aug. 28, 2024

Mitochondria exhibit heterogeneous shapes and networks within among cell types tissues, also in normal or osteoporotic bone tissues with complex types. This dynamic characteristic is determined by the high plasticity provided mitochondrial dynamics stemmed from responding to survival functional requirements of various cells a specific microenvironments. In contrast, dysfunction, induced dysregulation dynamics, may act as trigger death signals, including common apoptosis other forms programmed (PCD). These PCD processes consisting tightly structured cascade gene expression events, can further influence remodeling facilitating cells. Mitochondrial therefore, drive stand at crossroads life integrating external signals altering metabolism, shape, signal-response properties mitochondria. implies that targeting displays significant potential treatment osteoporosis. Considerable effort has been made osteoporosis emphasize parallel roles mitochondria regulating energy calcium signal transduction, oxidative stress, inflammation, death. However, emerging field dynamics-related not well understood. Herein, bridge gap, we outline latest knowledge on during

Language: Английский

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Nuclear factor erythroid 2-related factor-mediated signaling alleviates ferroptosis during cerebral ischemia-reperfusion injury

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117513 - 117513

Published: Sept. 27, 2024

Language: Английский

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Lactate Mediates Exercise-Induced Modulation of Mitophagy and Ferroptosis, Reducing Amyloid-Beta and Tau in Type 2 Diabetes: A Molecular Study

Published: Jan. 1, 2025

Background: This study examined the impact of lactate accumulation, induced by high-intensity interval training (HIIT), on reducing amyloid-beta (Aβ) and tau protein levels through enhanced mitophagy decreased ferroptosis in hippocampus type 2 diabetic rats.Methods: Thirty-two male Wistar rats were divided into four groups: control (Co), exercise (EX), diabetes (DB), with (DB + EX). Diabetes was DB EX groups via a high-fat diet followed streptozotocin injection (35 mg/kg). The performed treadmill-based HIIT, involving 4–10 running intervals at 80–100% Vmax. Serum hippocampal expression MCT2, SIRT1, BDNF, p62, Keap1, NRF2, MDA, GPX4, PINK1, parkin, Aβ, Tau assessed.Results: In group, Parkin elevated, while reduced compared to group.Conclusion: HIIT enhances reduces lactate-SIRT1-BDNF p62-Keap1-NRF2 pathways, potentially mitigating Aβ accumulation.

Language: Английский

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