Mitochondrial Cardiomyopathy: The Roles of mt-tRNA Mutations

Abstract

Mitochondria are important organelles whose primary role is generating energy through the oxidative phosphorylation (OXPHOS) system. Cardiomyopathy, a common clinical disorder, is frequently associated with pathogenic mutations in nuclear and mitochondrial genes. To date, a growing number of nuclear gene mutations have been linked with cardiomyopathy; however, knowledge about mitochondrial tRNAs (mt-tRNAs) mutations in this disease remain inadequately understood. In fact, defects in mt-tRNA metabolism caused by pathogenic mutations may influence the functioning of the OXPHOS complexes, thereby impairing mitochondrial translation, which plays a critical role in the predisposition of this disease. In this review, we summarize some basic knowledge about tRNA biology, including its structure and function relations, modification, CCA-addition, and tRNA import into mitochondria. Furthermore, a variety of molecular mechanisms underlying tRNA mutations that cause mitochondrial dysfunctions are also discussed in this article.

The Association Between Mitochondrial tRNAGlu Variants and Hearing Loss: A Case-Control Study

“…Nucleotide at positions 55 and 54 are often chemically modified and thus contribute to the structural and functional importance of mt-tRNA. 30 , 31 Therefore, it can be anticipated that the alteration of mt-tRNA structure by these variants may lead to the failure of mt-tRNA Glu metabolism.

Figure 4 Cloverleaf structure of mt-tRNA Glu gene, arrows indicated the positions of m.T14709C, m.A14693G, m.A14692G and m.A14683G variants.

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“…Nucleotide at positions 55 and 54 are often chemically modified and thus contribute to the structural and functional importance of mt-tRNA. 30,31 Therefore, it can be anticipated that the alteration of mt-tRNA structure by these variants may lead to the failure of mt-tRNA Glu metabolism.…”

Lack of Association of Mitochondrial tRNA(Leu) A3243G Mutation with Allergic Chronic Rhinosinusitis Pathogenesis in South Indian Population

“…to endothelial dysfunction, pro-atherogenic and proinflammation [12][13][14][15]. Moreover, the mitochondrial tRNA A3243G and 1555(G) mutation was also shown to be particularly impactful on the nervous system leading to neurological symptoms such as seizures and sensory neural hearing loss respectively [16,17].…”

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

“…Несмотря на то, что митохондриальная дисфункция вовлечена в патоморфогенез ГКМП, мутации генов митохондриальных белков изучены не так хорошо, как мутации белков саркомера. Обнаружение мутаций митохондриальной ДНК (мтДНК) у пациентов с ГКМП является сложной задачей в связи с наличием феномена гетероплазмии и вариабельности их фенотипического выражения [52,53]. У пациентов с ГКМП, ассоциированной с мутациями мтДНК, может наблюдаться ряд клинических особенностей, включая гипертрофию миокарда, аритмии, сердечную недостаточность и другие сердечно-сосудистые нарушения [54].…”