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Most recently, increasing evidence has shown that mitochondrial dysfunction caused by mitochondrial tRNA (mt\u2010tRNA) mutations plays a putative role in the pathogenesis of this disease, despite its pathophysiology remaining poorly understood. In this study, a novel 12265A&gt;G mutation in mt\u2010tRNA<jats:sup>Ser(AGY)<\/jats:sup> was identified from a Chinese pedigree with maternally inherited DCM, together with a known mt\u2010tRNA<jats:sup>Cys<\/jats:sup> 5821G&gt;A mutation. Interestingly, the novel m.12265A&gt;G mutation changed the well\u2010conserved adenosine at Position 73 (A73) to guanine (G73) at the 3\u2009<jats:sup>\u2032<\/jats:sup>\u2010end of the mt\u2010tRNA<jats:sup>Ser(AGY)<\/jats:sup> acceptor arm, while the G\u2010to\u2010A transition at 5821 occurred at the acceptor arm of mt\u2010tRNA<jats:sup>Cys<\/jats:sup>, disrupting conserved base pairing (G6\u2010C67). Transmitochondrial cybrid\u2010based study demonstrated that cell lines with m.12265A&gt;G and m.5821G&gt;A mutations showed impaired mitochondrial functions, including significant reductions in mitochondrial ATP, membrane potential, NAD<jats:sup>+<\/jats:sup>\/NADH ratio, mitochondrial DNA (mtDNA) content, mitochondrial transcription factor A (TFAM) mRNA expression levels, and respiratory chain enzyme Complex I and III activities, whereas the levels of reactive oxygen species (ROS), calcium ions (Ca<jats:sup>2+<\/jats:sup>), and lactate were enhanced in mutant cells compared to controls (<jats:italic>p<\/jats:italic> &lt; 0.05). Thus, the m.12265A&gt;G and m.5821G&gt;A mutations may affect mt\u2010tRNA metabolism and impair mitochondrial function, which is involved in DCM. Taken together, our study broadens the genotypic interpretation of mt\u2010tRNA mutations linked to disease.<\/jats:p>","DOI":"10.1155\/humu\/7888334","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:51:49Z","timestamp":1749203509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dilated Cardiomyopathy May Be Associated With a Novel Mitochondrial tRNA<sup>Ser(AGY)<\/sup> 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