SREBP1c‐Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells DOI Creative Commons
Xin Wang, Jie Zhou, Yuzhu Peng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Acute kidney injury (AKI) is a prevalent clinical syndrome with high morbidity and mortality. Accumulating studies suggest mitochondrial dysfunction as the typical characteristics key process of AKI, but underlying mechanism remains elusive. The YME1‐like 1 (YME1L1) ATPase, an inner membrane protein, screened identified to be downregulated in renal tubular epithelial cells various mouse models patients AKI. Dramatically, restoration YME1L1 expression significantly alleviates cisplatin‐induced AKI subsequent chronic disease (CKD) through attenuating via maintaining optic atrophy (OPA1)‐mediated energy metabolism homeostasis. Mechanistically, upregulated sterol regulatory element binding transcription factor 1c (SREBP1c) demonstrated responsible for cisplatin‐mediated transcriptional inhibition directly its promoter region. Moreover, methyltransferase‐like 3 (METTL3)‐mediated m6A modification enhances SREBP1c mRNA stability, thereby upregulating expression. Notably, both depletion tubule‐specific overexpression markedly ameliorate transition CKD. Taken together, these findings that METTL3‐mediated upregulation contributes progression CKD disrupting transcriptionally suppressing YME1L1. Targeting SREBP1c/YME1L1 signaling may serve novel therapeutic strategy against

Language: Английский

lncRNA Oip5-as1 inhibits excessive mitochondrial fission in myocardial ischemia/reperfusion injury by modulating DRP1 phosphorylation DOI Creative Commons
Xiaowei Niu, Jingjing Zhang,

Shuwen Hu

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: May 14, 2024

Abstract Background Aberrant mitochondrial fission, a critical pathological event underlying myocardial ischemia/reperfusion (MI/R) injury, has emerged as potential therapeutic target. The long non-coding RNA (lncRNA) Oip5-as1 is increasingly recognized for its regulatory roles, particularly in MI/R injury. However, precise mechanistic role modulating dynamics remains elusive. This study aims to elucidate the of regulating fission and evaluate against Methods To simulate vitro HL-1 cardiomyocytes were subjected hypoxia/reoxygenation (H/R). Lentiviral vectors employed achieve overexpression or knockdown cells by expressing shRNA targeting Oip5-as1, respectively. impact on was assessed using CCK-8 assay, flow cytometry, immunofluorescence staining, biochemical assays. injury induced mice ligating left anterior descending coronary artery. Conditional knockout generated CRISPR/Cas9 genome editing technology, while achieved via intramyocardial administration AAV9 vectors. In mice, evaluated through echocardiographic assessment, histopathological transmission electron microscopy. Furthermore, Western blotting, pull-down, immunoprecipitation, co-immunoprecipitation assays conducted investigate Oip5-as1’s mechanisms. Results expression levels are significantly decreased MI/R-injured myocardium. undergoing H/R attenuated excessive preserved functionality, reduced cellular apoptosis, exhibited opposite effects. mouse model diminished infarct size improved cardiac function. exacerbated dysfunction, which reversed treatment with division inhibitor-1 (Mdivi-1). Mechanistically, selectively interacts AKAP1 CaN proteins, inhibiting activation subsequent DRP1 dephosphorylation at Ser637, thereby constraining DRP1’s translocation mitochondria involvement fission. Conclusions Our underscores pivotal mitigating during findings not only enhance our comprehension molecular mechanisms but also identify target ameliorating Graphical

Language: Английский

Citations

6
Role of dynamin-related protein 1-dependent mitochondrial fission in drug-induced toxicity DOI Creative Commons
Dan Li, Yueyan Li, Wei Pan

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107250 - 107250

Published: June 13, 2024

Dynamin-related protein 1 (DRP1) is an essential controller of mitochondrial fission whose activity tightly controlled to ensure balanced dynamics and maintain internal cellular homeostasis. Growing evidence suggests that DRP1-dependent plays a role in drug-induced toxicity (DIT). Therefore, understanding the molecular mechanisms underlying DIT precise regulation DRP1 function will inform development potential therapeutic treatments for DIT. This review comprehensively summarizes diverse DITs their mechanism associated with discusses vivo vitro model studies protection targeting DRP1.

Language: Английский

Citations

5
The Essential Role of Mitochondrial Dynamics in Viral Infections DOI Open Access
Xujie Duan, Rui Liu, Wenjun Lan

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1955 - 1955

Published: Feb. 24, 2025

Mitochondria are dynamic organelles that play crucial roles in energy production, metabolic balance, calcium homeostasis, apoptosis, and innate immunity, key determinants of cell fate. They also targets for viral invasion the body. Many proteins target mitochondria, controlling mitochondrial morphology, metabolism, immune response, thereby achieving evasion, promoting their proliferation, accelerating infection process. Mitochondrial quality control is to maintaining normal physiological functions homeostasis. Dysregulation dynamics closely related development many diseases. New constantly being discovered. Viruses change by targeting mitochondria achieve a persistent state infection. Currently, understanding during limited. Research on impact provides foundation investigating pathogenesis infections, disease process, identifying potential therapeutic targets. This review focuses connection between priority areas research virus-mediated insight into regulation viruses explores means mitochondrial-mediated treatment

Language: Английский

Citations

0
Met-Exo attenuates pyroptosis in miniature pig liver IRI by improving mitochondrial quality control DOI
Lei Cao, P. Andy Li, Tao Liu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114437 - 114437

Published: March 10, 2025

Language: Английский

Citations

0
Role of Mitochondria in Reno-Cardiac Diseases: A Study of Bioenergetics, Biogenesis, and GSH Signaling in Disease Transition DOI Creative Commons
Jairo Lumpuy‐Castillo, Isabel Amador‐Martínez,

Miriam Díaz-Rojas

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103340 - 103340

Published: Sept. 6, 2024

Language: Английский

Citations

4
NDUFS3 alleviates oxidative stress and ferroptosis in sepsis induced acute kidney injury through AMPK pathway DOI
Y. Wang,

Wuyang Lv,

Xiaotong Ma

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113393 - 113393

Published: Oct. 18, 2024

Language: Английский

Citations

4
MG53 Deficiency Mediated Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease Via Impairing Mitochondrial Dynamics DOI
Liwei Liao, Ziwen Zheng, Mingming Deng

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Inhibition of Drp1-mediated mitochondrial fission by P110 ameliorates renal injury in diabetic nephropathy DOI
Ruchi Yue,

Ziyu Yan,

Hongchu Zha

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114342 - 114342

Published: March 3, 2025

Language: Английский

Citations

0
Mesenchymal cell-derived exosomes and miR-29a-3p mitigate renal fibrosis and vascular rarefaction after renal ischemia reperfusion injury DOI Creative Commons
Jing Huang, Lang Shi, Yifei Yang

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 12, 2025

Renal fibrosis and vascular rarefaction are significant complications of ischemia/reperfusion (I/R) injury. Human umbilical cord mesenchymal cell-derived exosomes (hucMSC-exos) have shown potential in mitigating these conditions. This study investigates the role miR-29a-3p its therapeutic effects on I/R-induced renal damage. Male C57BL/6 mice were subjected to unilateral ischemia for 28 min followed by reperfusion. Exosomes mimics/inhibitors injected into mice. function, histological analysis, molecular assays performed evaluate integrity. Exosome treatment significantly improved function reduced post-I/R. MiR-29a-3p was highly expressed hucMSC-exos but models. mimic reduced, while inhibitor exacerbated rarefaction. Collagen I TNFR1 identified as direct targets fibroblasts endothelial cells, respectively. overexpressing provided superior protection compared unmodified hucMSC-exos. HucMSC-exos, particularly those miR-29a-3p, potent against collagen I, highlighting therapy.

Language: Английский

Citations

0
Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy DOI Creative Commons

Z.C. Chen,

Rayk Behrendt,

Lennart Wild

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 19, 2025

Abstract Nucleic acids from both self- and non-self-sources act as vital danger signals that trigger immune responses. Critical illnesses such acute respiratory distress syndrome, sepsis, trauma ischemia lead to the aberrant cytosolic accumulation massive release of nucleic are detected by antiviral innate receptors in endosome or cytosol. Activation for deoxyribonucleic ribonucleic triggers inflammation, a major contributor morbidity mortality critically ill patients. In past decade, there has been growing recognition therapeutic potential targeting acid sensing critical care. This review summarizes current knowledge ischemia. Given extensive research on common pathological conditions like cancer, autoimmune disorders, metabolic disorders aging, we provide comprehensive summary beyond illness offer insights may inform its role conditions. Additionally, discuss strategies specifically target sensing. By examining sources, sensor activation function, well impact regulating these pathways across various diseases, highlight driving illness.

Language: Английский

Citations

0