Related Experiment Video
Updated: Jun 14, 2025
09:36
Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
Published on: December 22, 2023
1.1K
c-Src Is Responsible for Mitochondria-Mediated Arrhythmic Risk in Ischemic Cardiomyopathy
An Xie1, Gyeoung-Jin Kang1, Eun Ji Kim1
1Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, USA.
Circulation. Arrhythmia and Electrophysiology
|August 30, 2024
Summary
Myocardial infarction increases active c-Src, leading to mitochondrial calcium uptake, QT prolongation, and arrhythmia. Targeting c-Src or MCU may offer new antiarrhythmic strategies for ischemic cardiomyopathy.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Molecular Cardiology
Background:
- Mitochondrial calcium (Ca2+) uptake is linked to QT prolongation and arrhythmias in nonischemic cardiomyopathy.
- This study investigates the role of mitochondria in ischemic arrhythmic risk and identifies upstream regulators.
Purpose of the Study:
- To define the role of mitochondria in ischemic arrhythmic risk.
- To identify upstream regulators of mitochondrial Ca2+ handling in the context of myocardial infarction (MI).
Main Methods:
- Myocardial infarction (MI) induced in mice via coronary artery ligation.
- Utilized Western blot, immunoprecipitation, ECG telemetry, and patch-clamp techniques.
- Analyzed human heart tissues from patients with ischemic cardiomyopathy.
Main Results:
- MI increased active c-Src (proto-oncogene tyrosine-protein kinase Src) and tyrosine-phosphorylated MCU (mitochondrial Ca2+ uniporter).
- c-Src directly phosphorylated MCU, increasing mitochondrial Ca2+ uptake, action potential duration, and arrhythmias.
- Inhibition of c-Src or MCU reduced arrhythmias post-MI in mice and correlated with increased c-Src/MCU activity in human samples.
Conclusions:
- Increased active c-Src in MI leads to MCU phosphorylation, enhanced mitochondrial Ca2+ uptake, QT prolongation, and arrhythmia.
- c-Src and MCU represent potential novel therapeutic targets for antiarrhythmic strategies in ischemic heart disease.
More Related Videos
11:00Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
10.1K
09:16Isolation and Characterization of Cardiac Mesenchymal Stromal Cells from Endomyocardial Bioptic Samples of Arrhythmogenic Cardiomyopathy Patients
Published on: February 28, 2018
7.7K
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
12.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
12.3K
01:28Mechanism of Cardiac Arrhythmias
901
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
901
01:45Mitochondrial Membranes
9.3K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
9.3K
01:19Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
01:48ATP Synthase: Mechanism
14.2K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.2K
01:37Mitochondria
11.5K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
11.5K