The Binding of HSPA8 and Mitochondrial ALDH2 Mediates Oxygen-Glucose Deprivation-Induced Fibroblast Senescence DOI Creative Commons

Wenting Hui,

Tongtong Song,

Ling Yu

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 13(1), P. 42 - 42

Published: Dec. 25, 2023

Cellular senescence refers to the permanent and irreversible cessation of cell cycle. Recently, it has gained significant interest as a promising target for preventing cardiovascular diseases. Aldehyde dehydrogenase 2 (ALDH2) is mitochondrial enzyme that been closely linked with an increased risk In this study, bioinformatics analysis revealed signaling pathway fibroblast significantly activated in mice after myocardial infarction (MI), ALDH2 might be crucial molecule responsible inducing change. Therefore, we created NIH3T3 line oxygen-glucose deprivation (OGD) model replicate conditions MI vitro. We further decreased activity critical factor affects OGD, activation can improve damage caused by OGD. identified Heat Shock 70-kDa Protein 8 (HSPA8) interacting protein through co-immunoprecipitation (Co-IP) mass spectrometry (MS) detection. Subsequently, our studies showed HSPA8 translocates mitochondria potentially binding inhibiting its activity. By transfecting siRNA inhibit expression cells, was found increased, characteristics induced OGD cells improved. conclusion, data from study suggest HSPA8, conjunction ALDH2, could regulate deprivation, providing new direction foundation effectively intervening infarction.

Language: Английский

Mitochondrial dysfunction: mechanisms and advances in therapy DOI Creative Commons

Zong Yao,

Hao Li, Peng Liao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Language: Английский

Citations

239
Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases DOI Creative Commons
Zonghan Liu, Yi Sun, Zhengtang Qi

et al.

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: May 19, 2022

Mitochondria play a pivotal role in energy generation and cellular physiological processes. These organelles are highly dynamic, constantly changing their morphology, location, distribution response to stress. In recent years, the phenomenon of mitochondrial transfer has attracted significant attention interest from biologists medical investigators. Intercellular occurs different ways, including tunnelling nanotubes (TNTs), extracellular vesicles (EVs), gap junction channels (GJCs). According research on intercellular pathological environments, hold great potential for maintaining body homeostasis regulating Multiple groups have developed artificial transfer/transplantation (AMT/T) methods that healthy mitochondria into damaged cells recover function. This paper reviews spontaneous modes, mechanisms, latest AMT/T. Furthermore, application value mechanism AMT/T disease treatment also discussed.

Language: Английский

Citations

149
The role of aldehyde dehydrogenase 2 in cardiovascular disease DOI
Jian Zhang, Yunyun Guo, Xiangkai Zhao

et al.

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(7), P. 495 - 509

Published: Feb. 13, 2023

Language: Английский

Citations

72
Myocardial ischemia-reperfusion injury; Molecular mechanisms and prevention DOI
Yang Liu, Lei Li, Zhen Wang

et al.

Microvascular Research, Journal Year: 2023, Volume and Issue: 149, P. 104565 - 104565

Published: June 10, 2023

Language: Английский

Citations

58
Intravenous Transplantation of an Ischemic-specific Peptide-TPP-mitochondrial Compound Alleviates Myocardial Ischemic Reperfusion Injury DOI Creative Commons
Xiaolei Sun, Hang Chen, Rifeng Gao

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(2), P. 896 - 909

Published: Jan. 10, 2023

It is known that mitochondrial dysfunction a critical factor involved in myocardial ischemia–reperfusion injury. Mitochondrial transplantation has been suggested as an effective therapeutic strategy to protect against However, its clinical translation remains limited because it requires the local injection of mitochondria into myocardium. Here, polypeptide, CSTSMLKAC (PEP), bound triphenylphosphonium cations (TPP+) effectively binds form PEP–TPP–mitochondrial compound. Further investigation this compound revealed ischemia-sensing properties PEP promote translocation ischemic Additionally, targeting peptide, PEP, readily dissociates from compound, allowing for transplanted be efficiently internalized by cardiomyocytes or transferred endothelial cells. promotes cardiomyocyte energetics and mechanical contraction, subsequently reducing cellular apoptosis, macrophage infiltration, pro-inflammatory response, all which lead attenuation Thus, study provides promising evidence intravenous myocardium ameliorates

Language: Английский

Citations

55
Oral mitochondrial transplantation using nanomotors to treat ischaemic heart disease DOI
Ziyu Wu, Lin Chen,

Wenyan Guo

et al.

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(9), P. 1375 - 1385

Published: May 27, 2024

Language: Английский

Citations

33
Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition DOI Creative Commons
Kun Yang, Rifeng Gao, Hanchuan Chen

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(18), P. 1662 - 1680

Published: April 26, 2024

The Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene is closely associated with myocardial ischaemia/reperfusion injury (I/RI). effects of ALDH2 on neutrophil extracellular trap (NET) formation (i.e. NETosis) during I/RI remain unknown. This study aimed to investigate role NETosis pathogenesis I/RI.

Language: Английский

Citations

29
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies DOI Creative Commons
Kei Hayashida, Ryosuke Takegawa, Muhammad Shoaib

et al.

Journal of Translational Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: May 17, 2021

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in signaling and growth, facilitate cell death. Based on their multifactorial roles, mitochondria also critical the progression of illnesses. Transplantation has been reported as a potential promising approach to treat illnesses, particularly ischemia reperfusion injury (IRI). However, systematic review relevant literature not conducted date. Here, we systematically reviewed animal human studies IRI summarize evidence mitochondrial transplantation. Methods We searched MEDLINE, Cochrane library, Embase performed transplantation both preclinical clinical studies. developed search strategy using combination keywords Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer method were excluded. Data extracted tailored template, data synthesis was descriptive because suitable meta-analysis. Results Overall, identified 20 two Among studies, 14 (70%) focused either brain or heart IRI. Both autograft allograft used 17 (85%) The designs heterogeneous terms route administration, timing transplantation, dosage used. Twelve (60%) blinded manner. All markedly mitigated target tissues, but there variation biological biomarkers pathological changes. with single-arm, unblinded design, which autologous applied pediatric patients who required extracorporeal membrane oxygenation (ECMO) IRI–associated myocardial dysfunction after cardiac surgery. Conclusion gathered from our supports beneficial effects IRI, its translation remains limited. Further investigations thus explore mechanisms action patient outcomes settings Systematic registration study registered at UMIN under number UMIN000043347.

Language: Английский

Citations

69
Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives DOI Open Access
Marco D’Amato, Francesca Morra, Ivano Di Meo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1969 - 1969

Published: Jan. 19, 2023

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial (mtDNA). Current therapies still far from being fully effective and covering the broad spectrum of mtDNA. For example, unlike heteroplasmic conditions, MDs caused homoplasmic mtDNA do not yet benefit advances molecular approaches. An attractive method providing dysfunctional cells and/or tissues with healthy mitochondria is transplantation. In this review, we discuss what known about intercellular transfer methods used to both vitro vivo, provide an outlook on future therapeutic applications. Overall, containing wild-type copies could induce a shift even when variants present, aim attenuating preventing progression pathological clinical phenotypes. summary, transplantation challenging but potentially ground-breaking option for treatment various pathologies, although several questions remain be addressed before its application medicine.

Language: Английский

Citations

42
Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction DOI Creative Commons
Sudha Sharma, Papori Sharma,

Tara Bailey

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1555 - 1555

Published: Oct. 25, 2022

Reactive oxygen species (ROS), a by-product of aerobic life, are highly reactive molecules with unpaired electrons. The excess ROS leads to oxidative stress, instigating the peroxidation polyunsaturated fatty acids (PUFA) in lipid membrane through free radical chain reaction and formation most bioactive aldehyde, known as 4-hydroxynonenal (4-HNE). 4-HNE functions signaling molecule toxic product acts mainly by forming covalent adducts nucleophilic functional groups proteins, nucleic acids, lipids. mitochondria have been implicated site for generation adduction. Several studies clarified how affects mitochondria's functions, including bioenergetics, calcium homeostasis, mitochondrial dynamics. Our research group has shown that activates apoptosis-inducing factor (AIFM2) translocation facilitates apoptosis mice human heart tissue during anti-cancer treatment. Recently, we demonstrated deficiency SOD2 conditional-specific cardiac knockout mouse increases ROS, subsequent production inside adduction several respiratory complex proteins. Moreover, highlighted physiological HNE discussed their relevance pathophysiology current discoveries concerning effects on mitochondria.

Language: Английский

Citations

40