USP18 enhances dengue virus replication by regulating mitochondrial DNA release DOI Creative Commons
Jenn‐Haung Lai,

De‐Wei Wu,

Chien‐Hsiang Wu

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 17, 2023

Dengue virus (DENV) infection remains a challenging health threat worldwide. Ubiquitin-specific protease 18 (USP18), which preserves the anti-interferon (IFN) effect, is an ideal target through DENV mediates its own immune evasion. However, much of function and mechanism USP18 in regulating replication incompletely understood. In addition, whether regulates merely by causing IFN hyporesponsiveness not clear. present study, using several different approaches to block signaling, including neutralizing antibodies (Abs), anti-IFN receptor Abs, Janus kinase inhibitors alpha beta subunit 1 (IFNAR1)knockout cells, we showed that may regulate IFN-associated IFN-unassociated manners. Localized mitochondria, regulated release mitochondrial DNA (mtDNA) cytosol affect viral replication, mechanisms such as reactive oxygen species (mtROS) production, changes membrane potential, mobilization calcium into 8-oxoguanine glycosylase (OGG1) expression, oxidation fragmentation mtDNA, opening permeability transition pore (mPTP) were involved USP18-regulated mtDNA cytosol. We therefore identify machineries are association with effects.

Language: Английский

Genotype-specific precision tumor therapy using mitochondrial DNA mutation-induced drug release system DOI Creative Commons
Y Li, Ru Xu,

Yonghua Wu

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(39)

Published: Sept. 27, 2023

Precise killing of tumor cells without affecting surrounding normal is a challenge. Mitochondrial DNA (mtDNA) mutations, common genetic variant in cancer, can directly affect metabolic homeostasis, serving as an ideal regulatory switch for precise therapy. Here, we designed mutation-induced drug release system (MIDRS), using the single-nucleotide variation (SNV) recognition ability and trans-cleavage activity Cas12a to convert tumor-specific mtDNA mutations into intracellular release, realizing cell killing. Using Ce6 model drug, MIDRS enabled organelle-level photodynamic therapy, triggering innate adaptive immunity simultaneously. In vivo evaluation showed that MIDRSMT could identify tissue carrying SNVs unilateral, bilateral, heterogeneous models, producing excellent antitumor effect (~82.6%) thus resulting stronger systemic immune response. Additionally, was suitable genotype-specific precision chemotherapeutic drugs. This strategy holds promise mutation-specific personalized treatment approaches.

Language: Английский

Citations

12
Blocking reverse electron transfer-mediated mitochondrial DNA oxidation rescues cells from PANoptosis DOI

Fuli Shi,

Qing Li, Rong Xu

et al.

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 45(3), P. 594 - 608

Published: Nov. 14, 2023

Language: Английский

Citations

12
The cGAS‐STING‐related signature affects the prognosis of colorectal cancer through its regulation of multiple immune cells DOI Creative Commons
Yunlong Li,

Xunliang Jiang,

Hui Cao

et al.

IUBMB Life, Journal Year: 2025, Volume and Issue: 77(3)

Published: March 1, 2025

The cGAS-STING signaling pathway has emerged as a critical player in the immune response against cancer, including colorectal adenocarcinoma (COAD). Understanding impact of this on COAD at multiple omics levels is crucial for advancing cancer immunotherapy and precision medicine. This study aimed to investigate relationship between cGAS-STING-related genes COAD, analyzing gene mutations, copy number variations, DNA methylation, expression uncover pathway's influence prognosis. Utilizing multi-omics sequencing data from TCGA GEO databases, key core were identified further validated through PCR Western blot analysis. Mutations variations CASP8 RIPK1 genes, differential methylation patterns, mRNA specific assessed determine their Validation tissue samples highlighted NLRC3, CASP1, AIM2, CXCL10 pathway. Our findings demonstrate that mutations RIPK1, altered significantly prognosis COAD. identification pathway, particularly CXCL10, led development prognostic model predicting poor tumor outcomes cell infiltration. provides valuable insights into mechanisms offers potential directions future research

Language: Английский

Citations

0
Quality control of mitochondrial nucleoids DOI
Hao Liu,

Haixia Zhuang,

Du Feng

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges. DOI Creative Commons
Xavier Renaudin, Anna Campalans

DNA repair, Journal Year: 2025, Volume and Issue: 149, P. 103827 - 103827

Published: March 16, 2025

Oxidative DNA damage, resulting from endogenous cellular processes and external sources plays a significant role in mutagenesis, cancer progression, the pathogenesis of neurological disorders. Base Excision Repair (BER) is involved repair base modifications such as oxidations or alkylations well single strand breaks. The glycosylase OGG1, initiates BER pathway by recognition excision 8oxoG, most common oxidative lesion, both nuclear mitochondrial DNA. Beyond repair, OGG1 modulates transcription, particularly pro-inflammatory genes, linking damage to broader biological like inflammation aging. In therapy, inhibition has emerged promising strategy enhance treatment efficacy. Targeting sensitizes cells chemotherapies, radiotherapies, PARP inhibitors, presenting opportunities overcome therapy resistance. Additionally, activators hold potential mitigating associated with aging This review presents development several inhibitors how they have contributed advance our knowledge fundamental functions OGG1. We also discuss new provide for clinical applications treating cancer, Finally, we highlight challenges targeting regarding off-target effects recently reported some can these limitations.

Language: Английский

Citations

0
Mitochondrial DNA in Exercise-Mediated Innate Immune Responses DOI Open Access
Xin Wen,

Jingcheng Fan,

Xuemei Duan

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3069 - 3069

Published: March 27, 2025

Mitochondria are considered as "the plant of power" with cells for a long time. However, recent researches suggest that mitochondria also take part in innate immune response to great extent. Remarkably, mtDNA was reported have immunnostimulatory potential 2004. Since then, there has been rapid growth understanding the role immune. The is released into cytosol, extracellular environment, or circulating blood through BAK/BAX pore, mPTP, and GSDMD pore upon mitochondrial damage, where it recognized by PRRs including TLR9, cGAS, NLRP3, thereby triggering response. On other hand, regular exercise an effective intervention strategy Some studies show chronic moderate-intensity endurance exercise, resistance training, HIIT, acute enhance function promoting transcription replication, thus blunting abnormal release excessive contrary, high-intensity elicits opposite effect. Nevertheless, only very small body research far performed illustrate impact on mtDNA-driven response, overall review lacking. In light these, we summarize current knowledge mechanism mediating mtDNA, influence leakage, hoping pave way investigate new diagnostic therapeutic approaches immunopathies.

Language: Английский

Citations

0
The TWIK2-mtDNA-NLRP3 inflammasome signaling in hepatic macrophages facilitates exercise-induced attenuation of hepatic inflammation and insulin resistance in db/db mice DOI
Tan Zhang,

Jingcheng Fan,

Xin Wen

et al.

Journal of Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

0
Dual chemical labeling enables nucleotide-resolution mapping of DNA abasic sites and common alkylation damage in human mitochondrial DNA DOI Creative Commons
Chaoxing Liu, Brandon H. Le, Wenyan Xu

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(13), P. e73 - e73

Published: June 9, 2023

Mitochondrial DNA (mtDNA) modifications play an emerging role in innate immunity and inflammatory diseases. Nonetheless, relatively little is known regarding the locations of mtDNA modifications. Such information critically important for deciphering their roles instability, mtDNA-mediated immune responses, mitochondrial disorders. The affinity probe-based enrichment lesion-containing represents a key strategy sequencing Existing methods are limited specificity abasic (AP) sites, prevalent modification repair intermediate. Herein, we devise novel approach, termed dual chemical labeling-assisted (DCL-seq), mapping AP sites. DCL-seq features two designer compounds enriching sites specifically at single-nucleotide resolution. For proof principle, mapped from HeLa cells under different biological conditions. resulting site maps coincide with regions low TFAM (mitochondrial transcription factor A) coverage potential G-quadruplex-forming sequences. In addition, demonstrated broader applicability method other mtDNA, such as N7-methyl-2'-deoxyguanosine N3-methyl-2'-deoxyadenosine, when coupled lesion-specific enzyme. Together, holds promise to sequence multiple various samples.

Language: Английский

Citations

10
Therapeutic effect of mitochondrial transplantation on burn injury DOI
Zhen Li,

Xinhui Cao,

Zuohao Liu

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 215, P. 2 - 13

Published: Feb. 22, 2024

Language: Английский

Citations

3
Small molecule inhibitor binds to NOD-like receptor family pyrin domain containing 3 and prevents inflammasome activation DOI Creative Commons

Angela Lackner,

Julia Elise Cabral, Yanfei Qiu

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(8), P. 110459 - 110459

Published: July 5, 2024

Language: Английский

Citations

3