Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases DOI Creative Commons
Yi Luan, Ying Luan, Feng Qi

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

The normal function of the mitochondria is crucial for most tissues especially those that demand a high energy supply. Emerging evidence has pointed out healthy mitochondrial closely associated with heart function. When these processes fail to repair damaged mitochondria, cells initiate removal process referred as mitophagy clear away defective mitochondria. In cardiomyocytes, metabolic activity, cell differentiation, apoptosis, and other physiological involved in major phenotypic alterations. Mitophagy alterations may contribute detrimental or beneficial effects multitude cardiac diseases, indicating potential clinical insights after close understanding mechanisms. Here, we discuss current opinions progression such ischemic disease, diabetic cardiomyopathy, hypertrophy, failure, arrhythmia, focus on key molecules related pathways regulation mitophagy. We also recently reported approaches targeting therapy diseases.

Language: Английский

Mitophagy-related regulated cell death: molecular mechanisms and disease implications DOI Creative Commons

Molin Yang,

Xiang Wei, Xin Yi

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 16, 2024

Abstract During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject to stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular quality control homeostasis, with activation involving both ubiquitin-dependent ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected mitophagy. These diverse RCD been shown be by mitophagy implicated pathogenesis a variety diseases, such as tumors, degenerative ischemia‒reperfusion injury (IRI). Importantly, targeting regulate has excellent therapeutic potential preclinical trials, expected an effective strategy treatment related diseases. Here, we present summary role RCD, focus on molecular mechanisms which regulates RCD. We also discuss implications mitophagy-related context various

Language: Английский

Citations

16
Ferroptosis triggers mitochondrial fragmentation via Drp1 activation DOI Creative Commons
Lohans Pedrera,

Laura Prieto Clemente,

Alina Dahlhaus

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 25, 2025

Abstract Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved mediating constitutive fission cell death pathways. During ferroptosis, a recently identified type regulated necrosis driven by excessive lipid peroxidation, fragmentation observed. Yet, how this whether it ferroptotic remained unexplored. Here, we provide evidence that Drp1 activated upon experimental induction ferroptosis promotes execution fragmentation. Using time-lapse microscopy, found induced loss membrane potential, but not outer permeabilization. Importantly, accelerated kinetics. Notably, function was mediated the regulation dynamics, as overexpression Mitofusin 2 phenocopied effect deficiency delaying Mechanistically, phosphorylated after translocates to mitochondria. Further activation at mitochondria through phosphatase PGAM5 promoted death. Remarkably, depletion delayed plasma peroxidation. These data for functional role acceleration death, with important implications targeting diseases associated ferroptosis.

Language: Английский

Citations

3
SIRT5‐Related Desuccinylation Modification Contributes to Quercetin‐Induced Protection against Heart Failure and High‐Glucose‐Prompted Cardiomyocytes Injured through Regulation of Mitochondrial Quality Surveillance DOI Creative Commons
Xing Chang, Tian Zhang, Junyan Wang

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Myocardial fibrosis represents the primary pathological change associated with diabetic cardiomyopathy and heart failure, it leads to decreased myocardial compliance impaired cardiac diastolic systolic function. Quercetin, an active ingredient in various medicinal plants, exerts therapeutic effects against cardiovascular diseases. Here, we investigate whether SIRT5‐ IDH2‐related desuccinylation is involved underlying mechanism of failure while exploring related drugs for mitochondrial quality surveillance. Mouse models established by transverse aortic constriction (TAC), were administered quercetin (50 mg/kg) daily 4 weeks. HL‐1 cells pretreated treated high glucose (30 mM) vitro . Cardiac function, western blotting, quantitative PCR, enzyme‐linked immunosorbent assay, immunofluorescence analysis employed analyze surveillance, oxidative stress, inflammatory response cells, whereas IDH2 succinylation levels detected using immunoprecipitation. incidence increased after TAC, abnormal ejection Following high‐glucose treatment, cell activity was inhibited, causing excess production reactive oxygen species inhibition respiratory complex I/III antioxidant enzyme activity, as well stress response, imbalanced surveillance homeostasis, apoptosis. Quercetin inhibited improved function increasing energy metabolism regulating fusion/fission biosynthesis inhibiting injury. Additionally, TAC SIRT5 expression at level succinylation. However, promoted expression. Moreover, treatment si‐SIRT5 abolished protective effect on viability. Hence, may promote through SIRT5, maintain protect mouse cardiomyocytes under conditions, improve fibrosis, thereby reducing failure.

Language: Английский

Citations

74
[Retracted] Irisin Attenuates Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in the H9C2 Cellular Model of Septic Cardiomyopathy through Augmenting Fundc1‐Dependent Mitophagy DOI Creative Commons
Xiaoqing Jiang, Shumin Cai, Yinghui Jin

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

In the present study, we used lipopolysaccharide- (LPS-) stimulated H9C2 cardiomyocytes to investigate whether irisin treatment attenuates septic cardiomyopathy via Fundc1-related mitophagy. Fundc1 levels and mitophagy were significantly reduced in LPS-stimulated but increased by treatment. Irisin ATP production activities of mitochondrial complexes I III cardiomyocytes. also improved glucose metabolism LPS-induced reactive oxygen species increasing antioxidant enzymes, glutathione peroxidase (GPX), superoxide dismutase (SOD), as well (GSH). TUNEL assays showed that cardiomyocyte apoptosis suppressing activation caspase-3 caspase-9. However, beneficial effects on oxidative stress, metabolism, viability abolished silencing Fundc1. These results demonstrate abrogates dysfunction, through This suggests is a potentially useful for cardiomyopathy, though further investigations are necessary confirm our findings.

Language: Английский

Citations

73
Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine DOI Creative Commons
Lenka Koklesová, Alena Mazuráková, Marek Samec

et al.

The EPMA Journal, Journal Year: 2022, Volume and Issue: 13(2), P. 177 - 193

Published: May 12, 2022

Abstract Mitochondria are the “gatekeeper” in a wide range of cellular functions, signaling events, cell homeostasis, proliferation, and apoptosis. Consequently, mitochondrial injury is linked to systemic effects compromising multi-organ functionality. Although stress common for many pathomechanisms, individual outcomes differ significantly comprising spectrum associated pathologies their severity grade. highly ambitious task paradigm shift from reactive predictive, preventive, personalized medicine (PPPM/3PM) distinguish between disease predisposition progression under circumstances, resulting compromised health followed by mitigating measures tailored individualized patient profile. For successful implementation PPPM concepts, robust parameters essential quantify sustainability. The current article analyses added value Mitochondrial Health Index (MHI) Bioenergetic (BHI) as potential systems relevant development its Based on pathomechanisms related context primary, secondary, tertiary care, broad conditions can benefit quantification using MHI/BHI prototype be further improved. Following that: planned pregnancies (improved mother offspring health), suboptimal with reversible damage, life-style patterns metabolic syndrome(s) predisposition, multi-factorial conditions, genotoxic environment, ischemic stroke unclear aetiology, phenotypic aggressive cancer subtypes, premature aging neuro/degeneration, acute infectious diseases such COVID-19 pandemics, among others.

Language: Английский

Citations

62
PGAM5-Mediated PHB2 Dephosphorylation Contributes to Diabetic Cardiomyopathy by Disrupting Mitochondrial Quality Surveillance DOI Creative Commons
Rongjun Zou, Jun Tao, Jie He

et al.

Research, Journal Year: 2022, Volume and Issue: 2022

Published: Jan. 1, 2022

Disruption of the mitochondrial quality surveillance (MQS) system contributes to dysfunction in diabetic cardiomyopathy (DCM). In this study, we observed that cardiac expression phosphoglycerate mutase 5 (PGAM5), a Ser/Thr protein phosphatase, is upregulated mice with streptozotocin-induced DCM. Notably, DCM-related structural and functional deficits were negated cardiomyocyte-specific

Language: Английский

Citations

53
Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage DOI Creative Commons
Yihang Yu, Meiling Chen,

Qitong Guo

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Feb. 7, 2023

Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury death, leading acute kidney the transformation of chronic disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown promote injury. this preclinical study, we investigate role mechanism exosomes (HucMSC-Exos) on repair renal after injury.C57BL/6 mice underwent unilateral ureteral obstruction, was induced in HK-2 by cisplatin. HucMSC-Exos were assessed vivo vitro. The extent injury, activation necroptosis pathway, mitochondrial quality-control-related factors determined different groups. We also analyzed possible regulatory effector molecules transcriptomics.HucMSC-Exo inhibited promoted dephosphorylation S637 site Drp1 gene reducing expression PGAM5. This subsequently fission maintained functional homeostasis, mitigating promoting repair. addition, HucMSC-Exo displayed a targeting RIPK1 through miR-874-3p.The collective findings present study demonstrate that regulate miR-874-3p attenuate enhance repair, providing new therapeutic modalities ideas for AKI process CKD mitigate damage.

Language: Английский

Citations

41
Necroptosis in heart disease: Molecular mechanisms and therapeutic implications DOI Creative Commons
Xiaoyun Guo, Yi Chen, Qinghang Liu

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2022, Volume and Issue: 169, P. 74 - 83

Published: May 18, 2022

Language: Английский

Citations

40
Zishenhuoxue decoction-induced myocardial protection against ischemic injury through TMBIM6-VDAC1-mediated regulation of calcium homeostasis and mitochondrial quality surveillance DOI
Xing Chang, Siyuan Zhou, Jinfeng Liu

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 132, P. 155331 - 155331

Published: Dec. 31, 2023

Language: Английский

Citations

38
Sirtuin-3 activates the mitochondrial unfolded protein response and reduces cerebral ischemia/reperfusion injury DOI Creative Commons
Xiaowei Xie, Xu Qian,

Zhou Dingzhou

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(13), P. 4327 - 4339

Published: Jan. 1, 2023

Sirtuin-3 (Sirt3) deacetylates several mitochondrial proteins implicated into cerebral ischemia/reperfusion (I/R) injury. The unfolded protein response (UPRmt) favors proteostasis during various stressors. Here, we used Sirt3 transgenic mice and a transient middle artery occlusion model to evaluate the molecular basis of on UPRmt brain post-ischemic dysfunction. present study illustrated that abundance was suppressed in after ischemic abnormalities. Overexpression vivo infarction size attenuated neuroinflammation I/R overexpression restored neural viability by reducing ROS synthesis, maintaining potential improving adenosine triphosphate synthesis. protected neuronal mitochondria against malfunction via eliciting forkhead box O3 (Foxo3)/sphingosine kinase 1 (Sphk1) pathway. Inhibiting either or Foxo3/Sphk1 pathway relieved favorable influence function behavior. In contrast, Sphk1 sufficient reduce size, attenuate neuroinflammation, sustain prevent abnormalities post-ischemia Thus, protects homeostasis, Sirt3/Foxo3/Sphk1 is promosing therapeutic candidate for stroke.

Language: Английский

Citations

25