Screening for Mitochondrial tRNA Mutations in 318 Patients with Dilated Cardiomyopathy

Qi, Yujuan; Wu, Zhenhua; Bai, Yaobang; Jiao, Yan; Li, Peijun

doi:10.1159/000521615

Cited by 5 publications

(3 citation statements)

References 60 publications

(62 reference statements)

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“…The mitochondrial genome was a circular molecule containing 13 protein-encoding genes that contributed proteins to complexes I, III, IV, and V of the OXPHOS system, as well as 2 rRNAs and 22 tRNAs [43]. Point mutations in the genes encoding mt-tRNAs had been increasingly recognized as important causes of diseases; such variants can result in transcriptional and translational defects and consequently mitochondrial respiratory chain dysfunction [44][45][46]. Therefore, we hypothesized that mt-tRNA variants may play key roles in clinical expression of PE.…”

Section: Discussionmentioning

confidence: 99%

Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia

et al. 2022

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Objectives: Impairment of mitochondrial function caused by pathogenic mitochondrial DNA (mtDNA) mutations has been found to be associated with pre-eclampsia (PE). However, the underlying mechanism of PE remains poorly undetermined. The aim of this study is to evaluate the relationship between mitochondrial tRNAs (mt-tRNAs) variants and PE. Material and Methods: The mt-tRNAs variants in a cohort of 100 pregnant women with PE and 100 healthy subjects were examined by PCR-Sager sequencing. Moreover, the phylogenetic conservation analysis, mitochondrial haplogroup analysis, as well as pathogenicity scoring system were used to assess the potential pathogenicity of these tRNA variants. Results: We identified five possible pathogenic mt-tRNA variants: tRNAPhe A608G, tRNAIle A4263G, tRNAAla T5587C, tRNALeu(CUN) G12294C and tRNAPro G15995A. We noticed that these variants were not detected in control subjects and occurred at the positions which were extremely conserved. Alternations in tRNAs structure caused by these variants may lead to the failures in tRNAs metabolism, which may subsequently may lead to the impairment of mitochondrial translation, as well as the respiratory chain functions. Thus, mt-tRNA variants may be involved in the pathogenesis of PE. Conclusions: Taken together, our data indicated that variants in mt-tRNA genes were the important contributors to PE; screening for mt-tRNA variants was recommended for early detection and prevention of PE.

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Section: Discussionmentioning

confidence: 99%

Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia

et al. 2022

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“…A number of mutations in mtDNA have been identified in DCM. In an mt-tRNA mutation screen of 318 DCM cases, seven potentially pathogenic mutations were identified: MT-TL1 3302A>G, MT-TI 4295A>G, MT-TM 4435A>G, MT-TA 5655T>C, MT-TH 12201T>C, MT-TE14692A>G, and MT-TT 15927G>A [105]. Compared to control patients, patients carrying these mutations had significantly lower mtDNA copy numbers, reduced ATP production, and increased ROS production, which directly correlated with changes in energy reserves, oxidative stress, and MMP.…”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Mitochondrial Dysfunction in Cardiac Diseases and Therapeutic Strategies

Huang

Zhou

2023

Biomedicines

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Mitochondria are the main site of intracellular synthesis of ATP, which provides energy for various physiological activities of the cell. Cardiomyocytes have a high density of mitochondria and mitochondrial damage is present in a variety of cardiovascular diseases. In this paper, we describe mitochondrial damage in mitochondrial cardiomyopathy, congenital heart disease, coronary heart disease, myocardial ischemia–reperfusion injury, heart failure, and drug-induced cardiotoxicity, in the context of the key roles of mitochondria in cardiac development and homeostasis. Finally, we discuss the main current therapeutic strategies aimed at alleviating mitochondrial impairment-related cardiac dysfunction, including pharmacological strategies, gene therapy, mitochondrial replacement therapy, and mitochondrial transplantation. It is hoped that this will provide new ideas for the treatment of cardiovascular diseases.

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“…Following nsHCM, DCM is the next most common finding in MIC. DCM has been reported in both infantile and adult-onset MIC [ 100 , 101 ]. DCM may present as the primary cardiovascular manifestation or secondary to nsHCM.…”

Section: Mitochondrial Cardiomyopathymentioning

confidence: 99%

Mitochondrial Genome Variants as a Cause of Mitochondrial Cardiomyopathy

Campbell

Slone

Huang

2022

Cells

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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.

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Screening for Mitochondrial tRNA Mutations in 318 Patients with Dilated Cardiomyopathy

Cited by 5 publications

References 60 publications

Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia

Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia

Mitochondrial Dysfunction in Cardiac Diseases and Therapeutic Strategies

Mitochondrial Genome Variants as a Cause of Mitochondrial Cardiomyopathy

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