Mitophagy for cardioprotection

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Oct. 5, 2023

Abstract Mitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control including fusion and fission, degradation, biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are central organelle for maintaining cardiac function. Since adult cardiomyocytes humans rarely divide, number dysfunctional cannot easily be diluted through cell division. Thus, efficient degradation crucial to cellular Mitophagy, a specific form autophagy, major mechanism which damaged or unnecessary targeted eliminated. Mitophagy active at baseline response stress, plays an essential role cardiomyocytes. mediated multiple mechanisms heart, each these can partially compensate loss another mechanism. However, insufficient levels mitophagy eventually lead dysfunction development heart failure. In this review, we discuss molecular pathophysiology, with focus on recent findings field.

Language: Английский

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The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116337 - 116337

Published: Feb. 28, 2024

In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive lead to an increase in and ultimately exacerbate MIRI by causing overproduction uncontrolled production mitochondria. Phosphatase tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing (FUNDC1) B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators Pink1 Parkin mitochondrial surface proteins involved ubiquitin-dependent pathway, while BNIP3 FUNDC1 receptor non-ubiquitin-dependent which play crucial role maintaining homeostasis quality. These can induce inhibit protect against but may also trigger insufficient mitophagy, thereby worsening condition. Understanding actions these provide valuable insights into pathological mechanisms underlying development. Based on above background, this article reviews through Pink1/Parkin pathway mediated led BNIP3, as well related drug treatment, aim effective strategies for prevention treatment

Language: Английский

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The Emerging Role of m6A and Programmed Cell Death in Cardiovascular Diseases

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 247 - 247

Published: Feb. 8, 2025

N6-methyladenosine (m6A) is the most prevalent internal chemical modification in eukaryotic messenger RNA (mRNA), significantly impacting its lifecycle through dynamic and reversible processes involving methyltransferase, demethylase, binding proteins. These regulate mRNA stability, splicing, nuclear export, translation, degradation. Programmed cell death (PCD), a tightly controlled process encompassing apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, plays crucial role maintaining cellular homeostasis, tissue development, function. Recently, m6A has emerged as significant research area due to regulating PCD implications cardiovascular diseases (CVDs). In this review, we delve into intricate relationship between various types modification, emphasizing their pivotal roles initiation progression of CVDs such myocardial ischemia-reperfusion (I/R), atherosclerosis (AS), pulmonary hypertension (PH), cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity (DIC), heart failure (HF), infarction (MI). Our findings underscore potential elucidating CVD pave new pathways for prevention treatment strategies.

Language: Английский

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Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome

Life Sciences, Journal Year: 2024, Volume and Issue: 355, P. 122998 - 122998

Published: Aug. 20, 2024

Language: Английский

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YTHDF2 mediates the protective effects of MG53 on myocardial infarction injury via recognizing the m6A modification of MG53

Journal of Cardiothoracic Surgery, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 8, 2025

Language: Английский

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M⁶A reader protein YTHDF3 regulates cardiomyocyte death and atrophy by modulating the alternative splicing program

Published: April 16, 2025

Abstract Background The functional impact of m 6 A modifications on RNA is governed by reader proteins that read the marks and process accordingly. Recent studies have highlighted importance in heart. However, function a protein Ythdf3 heart remains completely unknown. Objective We aim to uncover hearts. Methods& Results Here, we show indispensable for heart, its knockdown leads cardiac cachexia evident cardiomyocyte atrophy, death, less dense myofibrils visualized electron microscopy. also found downregulation response doxorubicin, overexpression rescues doxorubicin-induced atrophy death. Contrary primarily cytoplasmic localization, localizes nucleus. Furthermore, using co-immunoprecipitation coupled with LC-MS/MS, interacts splicing like DDX5 HNRNPU regulates alternative Mechanistically, CaMKIIδ, an increase CaMKIIδA CaMKIIδC isoforms while decrease CaMKIIδ9 isoform. Conclusion Collectively, adult due alteration program.

Language: Английский

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Enhancement of YTHDF2 plays a protective role in acute IRI models through downregulation of TUG1 expression

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0319605 - e0319605

Published: April 24, 2025

As one of the major causes acute kidney injury, renal ischemia-reperfusion is a common health problem in series clinical situations, including transplantation. Although mechanisms IRI have been widely investigated, effective strategies are still lacking for its prevention and treatment. In previous study, we found that down-regulation taurine upregulated gene 1, long non-coding RNA (lncRNA TUG1), markedly alleviated through mitigating cell inflammation apoptosis. At meanwhile, YTHDF2, an methylation reading protein, was identified as vital player distinct organs, however, not reported kidney. We then conducted current study on function YTHDF2 regulatory role to TUG1. Based models vitro vivo, dramatical presented. Subsequently, exogenous perturbation protective effects apoptosis were demonstrated exogenous. Furthermore, with same model, it indicated protein negative regulated TUG1 via direction interaction. Since then, proved potential protector restraining further speculation, induction will possibly become possible strategy combat pathological process post transplantation or other conditions.

Language: Английский

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Placental RTN3L‐dependent ER‐Phagy Contributes to Fetal Testicular Dysplasia Upon Environmental Stress

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Abstract Prenatal environmental stress damages fetal testicular development, leading to male infertility. However, the precise mechanisms underlying impact of gestational on development require further investigation. This study demonstrates that stressor cadmium exposure caused placental estradiol synthesis inhibition and dysplasia. Gestational supplementation restores dysplasia by stress‐induced inhibition. Analysis human placentae cadmium‐stimulated primary trophoblasts confirmed ER‐phagy is associated with in placentae. Subsequently, data reveals significantly activates RTN3L‐mediated ER‐phagy. RTN3L ‐deficient cells Rtn3l ‐specific knockout mice confirm stress‐activated inhibited synthesis. Total N6‐methyladenosine level increasing stress‐exposed METTL3‐mediated modification suppression obviously restrains RTN3L‐dependent In conclusion, mRNA modification, inhibiting synthesis, contributing The early prevention treatment adult infertility from perspective fetal‐derived diseases.

Language: Английский

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Contribution and therapeutic value of mitophagy in cerebral ischemia-reperfusion injury after cardiac arrest

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115492 - 115492

Published: Sept. 15, 2023

Cardiopulmonary resuscitation and related life support technologies have improved substantially in recent years; however, mortality disability rates from cardiac arrest (CA) remain high are closely associated with the incidence of cerebral ischemia-reperfusion injury (CIRI), which is explained by a "double-hit" model (i.e., resulting both ischemia reperfusion). Mitochondria important power plants cell participate various biochemical processes, such as differentiation signaling eukaryotes. Various mitochondrial including energy metabolism, calcium homeostasis, free radical production, apoptosis, involved several stages progression development CIRI. Mitophagy key mechanism endogenous removal damaged mitochondria to maintain organelle function critical target for CIRI treatment after CA. also plays an essential role attenuating other organs, particularly during post-cardiac myocardial dysfunction. Regulation mitophagy may influence necroptosis (a programmed death pathway), main endpoint organ injury. In this review, we summarize pathways their regulatory proteins. New therapeutic methods drugs targeting animal models discussed. In-depth studies mechanisms underlying regulation will enhance our understanding damage repair processes CA, thereby contributing new strategies.

Language: Английский

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Unravelling the impact of RNA methylation genetic and epigenetic machinery in the treatment of cardiomyopathy

Pharmacological Research, Journal Year: 2024, Volume and Issue: 207, P. 107305 - 107305

Published: July 11, 2024

Cardiomyopathy (CM) represents a heterogeneous group of diseases primarily affecting cardiac structure and function, with genetic epigenetic dysregulation playing pivotal role in its pathogenesis. Emerging evidence from the burgeoning field epitranscriptomics has brought to light significant impact various RNA modifications, notably N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), 2′-O-methylation (Nm), 6,2′-O-dimethyladenosine (m6Am), on cardiomyocyte function broader processes vascular remodelling. These modifications have been shown influence key pathological mechanisms including mitochondrial dysfunction, oxidative stress, apoptosis, inflammation, immune response, myocardial fibrosis. Importantly, aberrations methylation machinery observed human CM cases animal models, highlighting critical methylating enzymes their potential as therapeutic targets or biomarkers for CM. This review underscores necessity deeper understanding context CM, illuminate novel avenues diagnostic tools, thereby addressing gap current management strategies this complex disease.

Language: Английский

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