Mitochondrial Dysfunction in Cardiac Arrhythmias
Abstract
1. Introduction
2. Basic Mechanisms of Arrhythmias
2.1. Phases of Action Potential (AP)
2.2. Abnormal Impulse Formation
2.2.1. Automaticity Disturbances
2.2.2. Triggered Activity
2.3. Conduction Disturbances
2.3.1. Reentry Tachycardia
2.3.2. Conduction Block
3. Mitochondrial Function and Dysfunction
4. Mitochondrial Dysfunction in Arrhythmogenic Pathogenesis
4.1. Sarcolemmal and Intracellular Ion Balance (Ca2+, Na+, K+)
4.1.1. Ca2+
4.1.2. Na+
4.1.3. K+
4.2. Mitochondria-Associated Proteins
4.2.1. Mitochondrial Ca2+ Transport Proteins
4.2.2. Connexin (Cx) Proteins
4.2.3. Mitochondrial RAS
4.2.4. MDPs
4.2.5. Mitochondrial GRKs and β-Arrestins
4.3. Inflammatory Signaling
4.4. Mitochondria-Associated ER Membranes (MAMs)
5. Mitochondrial Dysfunction in Different Arrhythmias
5.1. mtDNA and nDNA Mutation Associated Arrhythmias
5.2. SAN Dysfunction and AVN Dysfunction
5.3. Reentrant Tachyarrhythmias
5.3.1. AF
Electrical Stimulation-Induced AF
Aging-Associated Mitochondrial Dysfunction in AF
Gut Microbiota-Associated Mitochondrial Dysfunction in AF
Other Factors Induced AF
5.3.2. Ventricular Arrhythmias (VAs)
Cardiac Ischemia and I/R Injury-Induced VAs
Electrical Stimulation-Induced VAs
Other Factors Induced VA
5.3.3. Hereditary Muscular Dystrophy-Associated Arrhythmias
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inheritance Pattern | Clinical Syndrome | Mutations | Affected Genes/Proteins in Mitochondria | Arrhythmias Involved | Cardiac Manifestations | Other Systems Involved |
---|---|---|---|---|---|---|
Maternally Transmitted | Myoclonic epilepsy with ragged red fibers (MERRF) [35,36] | m.8344 A to G, m.8356 T to C, m.8363 G to A, and m.8361 G to A | MT-TK | Pre-excitation | Dilated and histiocytoid cardiomyopathy | Myoclonus, spasticity, myopathy |
Maternally Transmitted | Leber hereditary optic neuropathy [37] | m.3460 G to A, m.11778 G to A, and m.14484 T to C | MT-ND1, MT-ND4, MT-ND4L, or MT-ND6 | Sudden death | Dilated cardiac myopathy | Loss of vision |
Maternally Transmitted/Sporadic | Neuropathy, ataxia, and retinitis pigmentosa (NARP) [38,39] | m.8993 T to G | MT-ATP6 | Conduction block | Cardiomyopathy | Psychomotor retardation, epilepsy, ataxia, neuropathy, and myopathy |
Maternally Transmitted | Leigh syndrome (Mt DNA associated subtype) [40] | More than 75 monogenic causes | MT-TL-1, MT-TK, MT-TI | Conduction block | Hypertrophic cardiomyopathy | Psychomotor regression, respiratory failure, muscular and movement disorder (death at young age) |
Maternally Transmitted/Sporadic | Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) [41] | m.3243 A to G mutation in MT-TL-1 | MT-TL1, MT-TK, and MT-TE genes provide instructions for making tRNAs | Pre-excitation, bundle branch block | Dilated/hypertrophic cardiomyopathy | Severe encephalopathy, lactic acidosis, myoclonus |
Maternally Transmitted/Sporadic | Kearns–Sayre syndrome [42,43] | 4.9 kb Mt DNA deletion (12 genes)/point mutation | Not determined, involved in mitochondrial protein expression and oxidative phosphorylation | Atrioventricular conduction defects | Cardiomyopathy, syncope, Adams–Stokes syndrome, sudden cardiac death | Anemia, myopathy, lactic acidosis, CNS abnormality, endocrine abnormality, renal disease, sensorineural deafness, and retinal involvement |
X-Linked Recessive | Barth syndrome [44] | Mutations or deletions of the highly conserved Xq28 tafazzin (TAZ) gene | Tafazzin protein is essential for remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane | Ventricular arrhythmia, sudden cardiac death, prolonged QTc interval | Dilated/hypertrophic cardiomyopathy, endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC) | Skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA) |
Autosomal Recessive | Friedreich’s Ataxia[45] | GAA triplet repeat expansion in the first intron Frataxin (FXN) gene, silencing the gene | Frataxin: expressed in the mitochondria of tissue with high metabolic rates, involved in assembly of iron-sulfur clusters | Conduction block, atrial fibrillation, atrial/ventricular tachycardias, ECG repolarization abnormalities | Hypertrophic cardiomyopathy, heart failure | Gait and limb ataxia, dysarthria, loss of lower limb reflexes, optic neuropathy |
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Deng, J.; Jiang, Y.; Chen, Z.B.; Rhee, J.-W.; Deng, Y.; Wang, Z.V. Mitochondrial Dysfunction in Cardiac Arrhythmias. Cells 2023, 12, 679. https://doi.org/10.3390/cells12050679
Deng J, Jiang Y, Chen ZB, Rhee J-W, Deng Y, Wang ZV. Mitochondrial Dysfunction in Cardiac Arrhythmias. Cells. 2023; 12(5):679. https://doi.org/10.3390/cells12050679
Chicago/Turabian StyleDeng, Jielin, Yunqiu Jiang, Zhen Bouman Chen, June-Wha Rhee, Yingfeng Deng, and Zhao V. Wang. 2023. "Mitochondrial Dysfunction in Cardiac Arrhythmias" Cells 12, no. 5: 679. https://doi.org/10.3390/cells12050679
APA StyleDeng, J., Jiang, Y., Chen, Z. B., Rhee, J.-W., Deng, Y., & Wang, Z. V. (2023). Mitochondrial Dysfunction in Cardiac Arrhythmias. Cells, 12(5), 679. https://doi.org/10.3390/cells12050679