Mitochondrial Genome Variants as a Cause of Mitochondrial Cardiomyopathy
- PMID: 36139411
- PMCID: PMC9496904
- DOI: 10.3390/cells11182835
Mitochondrial Genome Variants as a Cause of Mitochondrial Cardiomyopathy
Abstract
Mitochondria are small double-membraned organelles responsible for the generation of energy used in the body in the form of ATP. Mitochondria are unique in that they contain their own circular mitochondrial genome termed mtDNA. mtDNA codes for 37 genes, and together with the nuclear genome (nDNA), dictate mitochondrial structure and function. Not surprisingly, pathogenic variants in the mtDNA or nDNA can result in mitochondrial disease. Mitochondrial disease primarily impacts tissues with high energy demands, including the heart. Mitochondrial cardiomyopathy is characterized by the abnormal structure or function of the myocardium secondary to genetic defects in either the nDNA or mtDNA. Mitochondrial cardiomyopathy can be isolated or part of a syndromic mitochondrial disease. Common manifestations of mitochondrial cardiomyopathy are a phenocopy of hypertrophic cardiomyopathy, dilated cardiomyopathy, and cardiac conduction defects. The underlying pathophysiology of mitochondrial cardiomyopathy is complex and likely involves multiple abnormal processes in the cell, stemming from deficient oxidative phosphorylation and ATP depletion. Possible pathophysiology includes the activation of alternative metabolic pathways, the accumulation of reactive oxygen species, dysfunctional mitochondrial dynamics, abnormal calcium homeostasis, and mitochondrial iron overload. Here, we highlight the clinical assessment of mtDNA-related mitochondrial cardiomyopathy and offer a novel hypothesis of a possible integrated, multivariable pathophysiology of disease.
Keywords: calcium; dilated cardiomyopathy; ferroptosis; hypertrophic cardiomyopathy; iron overload; mitochondrial cardiomyopathy; mitochondrial genome; mtDNA; reactive oxygen species.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9496904/bin/cells-11-02835-g001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9496904/bin/cells-11-02835-g002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9496904/bin/cells-11-02835-g003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9496904/bin/cells-11-02835-g004.gif)
Similar articles
-
Significance of Mitochondria DNA Mutations in Diseases.Adv Exp Med Biol. 2017;1038:219-230. doi: 10.1007/978-981-10-6674-0_15. Adv Exp Med Biol. 2017. PMID: 29178079 Review.
-
Progress in Molecular Genetic Study of Mitochondrial Cardiomyopathy.Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2017 Jun 20;39(3):438-444. doi: 10.3881/j.issn.1000-503X.2017.03.024. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2017. PMID: 28695818 Review.
-
The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement.Gene. 2005 Jul 18;354:169-80. doi: 10.1016/j.gene.2005.05.001. Gene. 2005. PMID: 16024186 Review.
-
Animal models for mitochondrial disease.Methods Mol Biol. 2002;197:3-54. doi: 10.1385/1-59259-284-8:003. Methods Mol Biol. 2002. PMID: 12013805 Review.
-
Mouse models for mitochondrial disease.Am J Med Genet. 2001 Spring;106(1):71-93. doi: 10.1002/ajmg.1393. Am J Med Genet. 2001. PMID: 11579427 Review.
Cited by
-
Successful transcatheter mitral valve repair for functional mitral regurgitation in a patient with mitochondrial cardiomyopathy: a case report.Eur Heart J Case Rep. 2023 Sep 1;7(9):ytad440. doi: 10.1093/ehjcr/ytad440. eCollection 2023 Sep. Eur Heart J Case Rep. 2023. PMID: 37705944 Free PMC article.
-
Mitochondrial Dysfunction in Cardiac Diseases and Therapeutic Strategies.Biomedicines. 2023 May 22;11(5):1500. doi: 10.3390/biomedicines11051500. Biomedicines. 2023. PMID: 37239170 Free PMC article. Review.
-
Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases.J Transl Med. 2023 May 25;21(1):347. doi: 10.1186/s12967-023-04203-6. J Transl Med. 2023. PMID: 37231493 Free PMC article. Review.
-
Expanding DdCBE-mediated targeting scope to aC motif preference in rat.Mol Ther Nucleic Acids. 2023 Feb 26;32:1-12. doi: 10.1016/j.omtn.2023.02.028. eCollection 2023 Jun 13. Mol Ther Nucleic Acids. 2023. PMID: 36942261 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical