CKLF induces microglial activation via triggering defective mitophagy and mitochondrial dysfunction

Autophagy, Год журнала: 2023, Номер 20(3), С. 590 - 613

Опубликована: Ноя. 1, 2023

Although microglial activation is induced by an increase in chemokines, the role of mitophagy this process remains unclear. This study aimed to elucidate CKLF/CKLF1 (chemokine-like factor 1)-induced and neuroinflammation, as well underlying molecular mechanisms following CKLF treatment. determined that CKLF, inducible chemokine brain, leads markers, such DNM1L, PINK1 (PTEN putative kinase 1), PRKN, OPTN, along with a simultaneous autophagosome formation, evidenced elevated levels BECN1 MAP1LC3B (microtubule-associated protein 1 light chain 3 beta)-II. However, SQSTM1, substrate autophagy, was also accumulated treatment, suggesting flux reduced mitophagosomes accumulated. These findings were confirmed transmission electron microscopy confocal microscopy. The defective observed our caused impaired lysosomal function, including mitophagosome-lysosome fusion, lysosome generation, acidification, resulting accumulation damaged mitochondria cells. Further analysis revealed pharmacological blocking or gene-silencing inhibited CKLF-mediated activation, expression marker AIF1 (allograft inflammatory 1) mRNA proinflammatory cytokines (Tnf Il6). Ultimately, results brains adult mice. In summary, induces mitophagy, inflammation, providing potential approach for treating neuroinflammatory diseases.

Язык: Английский

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Regulated cell death‐amplified sonodynamic anti‐tumor immune nanotherapeutics

BMEMat, Год журнала: 2024, Номер unknown

Опубликована: Март 4, 2024

Abstract Nanomedicine‐assisted sonodynamic therapy (SDT) has emerged as one of the most promising cancer therapies due to its unique advantages high penetration, non‐radiation, and excellent oxidative stress effect, but always suffered from self‐protection mechanism apoptosis resistance characteristics evolutionarily mutated cells. Regulated cell death (RCD) received increasing attention in precision treatments because significant role synergistically sensitizing reversing immunosuppressive microenvironment during SDT nanomedicine‐triggered immunogenic death. Herein, paradigmatic research RCD‐augmented tumor immunotherapeutics are typically introduced, such autophagy blockade, ferroptosis targeting, pyroptosis induction, necroptosis initiation, cuproptosis actuation, PANoptosis trigger, coordinated anti‐tumor mechanisms discussed detail. Multiple analysis focusing on currently unsolved problems future development prospects RCD‐based nano‐oncology medicine also prospected further strengthen expand scope therapeutic applications.

Язык: Английский

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FDX1 downregulation activates mitophagy and the PI3K/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production

Redox Biology, Год журнала: 2024, Номер 75, С. 103302 - 103302

Опубликована: Авг. 6, 2024

Mitochondrial dysfunction and metabolic reprogramming can lead to the development progression of hepatocellular carcinoma (HCC). Ferredoxin 1 (FDX1) is a small mitochondrial protein recent studies have shown that FDX1 plays an important role in tumor cuproptosis, but its HCC still elusive. In this study, we aim investigate expression novel functions HCC.

Язык: Английский

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Complex roles of autophagy in cancer development, immune evasion, and drug resistance

Drug Resistance Updates, Год журнала: 2024, Номер 78, С. 101170 - 101170

Опубликована: Ноя. 15, 2024

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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Macrophage polarization and its impact on idiopathic pulmonary fibrosis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 26, 2024

Idiopathic pulmonary fibrosis (IPF) is a lung disease that worsens over time, causing in the lungs and ultimately resulting respiratory failure high risk of death. Macrophages play crucial role immune system, showing flexibility by transforming into either pro-inflammatory (M1) or anti-inflammatory (M2) macrophages when exposed to different stimuli, impacting development IPF. Recent research has indicated polarization onset progression M1 secrete inflammatory cytokines agents early damage fibrosis, while M2 support tissue healing releasing cytokines. Developing novel treatments for IPF relies on thorough comprehension processes involved macrophage The review outlines regulation its impact IPF, with goal investigating possible therapeutic benefits advancement

Язык: Английский

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Targeting mitochondrial quality control: new therapeutic strategies for major diseases

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Авг. 21, 2024

Abstract Mitochondria play a crucial role in maintaining the normal physiological state of cells. Hence, ensuring mitochondrial quality control is imperative for prevention and treatment numerous diseases. Previous reviews on this topic have however been inconsistencies lack systematic organization. Therefore, review aims to provide comprehensive overview explore possibility targeting same major This systematically summarizes three fundamental characteristics control, including morphology dynamics, function metabolism, protein expression regulation. It also extensively examines how imbalances are linked diseases, such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, tumors. Additionally, explores innovative approaches target using small molecule drugs that regulate critical steps quality, nanomolecular materials designed precise mitochondria, novel cellular therapies, vesicle therapy transplantation. offers perspective comprehending shared mechanisms underlying occurrence progression diseases provides theoretical support practical guidance clinical implementation therapeutic strategies treating

Язык: Английский

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Mitochondrial dynamics and mitochondrial autophagy: Molecular structure, orchestrating mechanism and related disorders

Mitochondrion, Год журнала: 2024, Номер 75, С. 101847 - 101847

Опубликована: Янв. 19, 2024

Mitochondrial dynamics and autophagy play essential roles in normal cellular physiological activities, while abnormal mitochondrial can cause cancer related disorders. Abnormal usually occur parallel with autophagy. Both have been reported to a synergistic effect therefore complement or inhibit each other. Progress has made understanding the classical PINK1/Parkin pathway dynamical abnormalities. Still, mechanisms regulatory pathways underlying interaction between mitophagy remain unexplored. Like other existing reviews, we review molecular structure of proteins involved autophagy, how their abnormalities lead development diseases. We will also individual effects leading proliferation, differentiation invasion. In addition, explore contribute targeted precise regulation function. Through study mechanisms, as well role early disease development, effective targets for function be proposed enable accurate diagnosis treatment associated

Язык: Английский

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Soy isoflavones induces mitophagy to inhibit the progression of osteosarcoma by blocking the AKT/mTOR signaling pathway

Molecular Medicine, Год журнала: 2024, Номер 30(1)

Опубликована: Янв. 8, 2024

Abstract Background Soy isoflavones (SI) is a natural bioactive substance exhibiting beneficial effects on human health. This study aims to elucidate the therapeutic potential of SI in treatment osteosarcoma (OS) and investigate underlying mechanisms, particularly focusing mitophagy. Methods The proliferation, apoptosis, migration, invasion U2OS cells were analyzed. Mitophagy was assessed through multiple parameters: mitochondrial autophagosomes, membrane potential, autophagy-related proteins, reactive oxygen species (ROS), consumption rate (OCR). Protein levels related autophagy, AKT/mTOR pathway analyzed using western blot. efficacy further identified mouse tumor xenograft model. Cell apoptosis proliferation xenografts detected by TUNEL staining immunohistochemistry (IHC), respectively. Results dose-dependently suppressed viability, colony formation, cells, enhanced apoptosis. also induced mitophagy OS evidenced an increase autophagosomes ROS levels, decrease OCR, concomitant changes proteins. Mdivi-1, inhibitor mitophagy, reversed anti-tumor cells. In addition, blocked SC-79, AKT agonist, effect inducing Moreover, promoted cell vivo . Conclusions induces blocking pathway, contributing inhibition OS.

Язык: Английский

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Mitochondria-Targeted Multifunctional Nanoprodrugs by Inhibiting Metabolic Reprogramming for Combating Cisplatin-Resistant Lung Cancer

ACS Nano, Год журнала: 2024, Номер 18(32), С. 21156 - 21170

Опубликована: Авг. 1, 2024

How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The mechanism platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) glycolysis develop chemotherapy through metabolic variability. In addition, due lack histone protection relatively weak repair ability, (mtDNA) more susceptible damage, which in turn affects OXPHOS become potential target for drugs. Therefore, mitochondria, as targets anticancer drugs, have hot topic research. This study constructed self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. β-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles CD44 on surface further deliver intracellular mitochondria triphenylphosphine group (TPP+). Disulfide bonds be selectively degraded by glutathione (GSH) releasing lonidamine (LND) (Pt(IV)). Under action GSH ascorbic acid, Pt(IV) reduced (Pt(II)). Cisplatin cause mtDNA induce dysfunction mitophagy, then affect OXPHOS. Meanwhile, LND reduce hexokinase II (HK II) level, destruction block energy supply inhibition. Ultimately, this nano targeted synergistically kill cisplatin-resistant lung cancer cells, supplies an overcome choice via disrupt therapy.

Язык: Английский

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