Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of trans-Golgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355232 | PMC |
| http://dx.doi.org/10.1172/JCI122035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
β2-Adrenergic Receptor Agonist Clenbuterol Protects Against Acute Ischemia/Reperfusion-Induced Arrhythmia by Regulation of Akt/eNOS/NO/Cx43 Signaling Pathway.
Pharmacol Res Perspect
February 2025
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ventricular arrhythmias induced by ischemia/reperfusion injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction. This study investigated the protective effects of the β2-adrenergic receptor (β2-AR) agonist clenbuterol against ischemia/reperfusion-induced arrhythmias and the underlying mechanism. Anesthetized rats were subjected to 10-min left coronary artery occlusion and 10-min reperfusion in vivo.
View Article and Find Full Text PDFPrevalence and Prognostic Impact of ST Segment Elevation in Lead aVR Among Patients with Cardiac Arrest.
Eur Heart J Acute Cardiovasc Care
January 2025
Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT.
Background: In acute coronary syndrome, ST-segment elevation in lead aVR (STE-aVR) indicates global myocardial ischemia, often related to multivessel or severe left main disease, and correlates with increased mortality. The prevalence and prognostic significance of STE-aVR in cardiac arrest (CA) patients is unknown.
Methods: We identified patients (≥18 years) with CA between 2011 to 2022 who achieved return of spontaneous circulation (ROSC).
Effects of Isoproterenol Administration in Dobutamine Stress Echocardiography.
Echocardiography
February 2025
Department of Cardiology, MedStar Georgetown University Hospital, Washington, DC, USA.
Objective: This study evaluated the safety and efficacy of isoproterenol administration as an adjunct for achievement of target heart rate (HR) during dobutamine stress echocardiography (DSE).
Background: In DSE, optimal accuracy is achieved when a target HR of 85% of maximal predicted heart rate (MPHR) is attained. Although rarely studied, intravenous isoproterenol has been used as an adjunct therapy to dobutamine and atropine to increase chronotropic response during pharmacologic stress testing.
Mitigating PM Induced Myocardial Metal Deposition Through Sodium Thiosulfate Resulted in Reduction of Cardiotoxicity and Physiological Recovery From Ischemia-Reperfusion via Mitochondrial Preservation.
Environ Toxicol
January 2025
Cardiovascular Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
The cardiovascular risks linked to PM include calcification in both vasculature and myocardial tissues, leading to structural changes and functional decline. Through the selection of a clinically proven endogenous agent, sodium thiosulfate (STS), capable of addressing PM related cardiac abnormalities, we not only address the absence of effective solutions to mitigate PM toxicity, but also provide evidence for the repurposing potential of STS in ameliorating PM induced cardiac damage. Female Wistar rats were exposed to PM (250 μg/m) for 3 h daily for 21 days.
View Article and Find Full Text PDFMitochondrial transplantation for the treatment of cardiac and noncardiac diseases: mechanisms, prospective, and challenges.
Life Med
April 2024
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Mitochondrial transplantation (MT) is a promising therapeutic strategy that involves introducing healthy mitochondria into damaged tissues to restore cellular function. This approach has shown promise in treating cardiac diseases, such as ischemia-reperfusion injury, myocardial infarction, and heart failure, where mitochondrial dysfunction plays a crucial role. Transplanting healthy mitochondria into affected cardiac tissue has resulted in improved cardiac function, reduced infract size, and enhanced cell survival in preclinical studies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!