{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:02:34Z","timestamp":1788465754794,"version":"build-2803163510"},"reference-count":158,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013209","name":"\u201c3rd Call for H.F.R.I.\u2019s Research Projects to Support Faculty Members and Researchers\u201d","doi-asserted-by":"publisher","award":["25183"],"award-info":[{"award-number":["25183"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial tRNA genes are critical hotspots for pathogenic mutations and several mitochondrial diseases. They account for approximately 70\u201375% of disease-causing mtDNA variants despite comprising only 5\u201310% of the mitochondrial genome. These mutations interfere with mitochondrial translation and affect oxidative phosphorylation, resulting in remarkably heterogeneous multisystem disorders. Under this light, we systematically reviewed PubMed, Scopus, and MITOMAP databases through October 2025, indexing all clinically relevant pathogenic mt-tRNA mutations classified by affected organ systems and underlying molecular mechanisms. Approximately 500 distinct pathogenic variants were identified across all 22 mt-tRNA genes. Beyond typical syndromes like MELAS, MERRF, Leigh syndrome, and Kearns\u2013Sayre syndrome that are linked to mt-tRNA mutations, they increasingly implicate cardiovascular diseases (cardiomyopathy, hypertension), neuromuscular disorders (myopathies, encephalopathies), sensory impairment (hearing loss, optic neuropathy), metabolic dysfunction (diabetes, polycystic ovary syndrome), renal disease, neuropsychiatric conditions, and cancer. Beyond sequence mutations, defects in post-transcriptional modification systems emerge as critical disease mechanisms affecting mt-tRNA function and stability. The mutations on tRNA genes described herein represent potential targets for emerging genome editing therapies, although several translational challenges remain. However, targeted correction of pathogenic mt-tRNA mutations holds transformative potential for precision intervention on mitochondrial diseases.<\/jats:p>","DOI":"10.3390\/ijms262412023","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mitochondrial tRNA-Derived Diseases"],"prefix":"10.3390","volume":"26","author":[{"given":"Antonia","family":"Petropoulou","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Kypraios","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Rizopoulou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-2349","authenticated-orcid":false,"given":"Adamantia","family":"Kouvela","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Maniatis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Anastasopoulou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Anastogianni","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Korfiatis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6569-1928","authenticated-orcid":false,"given":"Katerina","family":"Grafanaki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"},{"name":"Department of Dermatology, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4900-5796","authenticated-orcid":false,"given":"Vassiliki","family":"Stamatopoulou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5699-4118","authenticated-orcid":false,"given":"Constantinos","family":"Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S0006-291X(05)80860-5","article-title":"A Point Mutation in the Mitochondrial tRNALeu(UUR) Gene in Melas (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like Episodes)","volume":"173","author":"Kobayashi","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/0092-8674(90)90059-N","article-title":"Myoclonic Epilepsy and Ragged-Red Fiber Disease (MERRF) Is Associated with a Mitochondrial DNA tRNALys Mutation","volume":"61","author":"Shoffner","year":"1990","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1101\/gad.1956510","article-title":"tRNA Biology Charges to the Front","volume":"24","author":"Phizicky","year":"2010","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hurto, R.L. (2011). Unexpected Functions of tRNA and tRNA Processing Enzymes. RNA Infrastructure and Networks, Springer.","DOI":"10.1007\/978-1-4614-0332-6_9"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tuller, T. (2012). The Effect of Dysregulation of tRNA Genes and Translation Efficiency Mutations in Cancer and Neurodegeneration. Front. Genet., 3.","DOI":"10.3389\/fgene.2012.00201"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/290457a0","article-title":"Sequence and Organization of the Human Mitochondrial Genome","volume":"290","author":"Anderson","year":"1981","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.mito.2006.01.005","article-title":"Identification and Sizing of GAA Trinucleotide Repeat Expansion, Investigation for D-Loop Variations and Mitochondrial Deletions in Iranian Patients with Friedreich\u2019s Ataxia","volume":"6","author":"Houshmand","year":"2006","journal-title":"Mitochondrion"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Abbott, J.A., Francklyn, C.S., and Robey-Bond, S.M. (2014). Transfer RNA and Human Disease. Front. Genet., 5.","DOI":"10.3389\/fgene.2014.00158"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/humu.22307","article-title":"Transition to Next Generation Analysis of the Whole Mitochondrial Genome: A Summary of Molecular Defects","volume":"34","author":"Tang","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dabravolski, S.A., Khotina, V.A., Sukhorukov, V.N., Kalmykov, V.A., Mikhaleva, L.M., and Orekhov, A.N. (2022). The Role of Mitochondrial DNA Mutations in Cardiovascular Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020952"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.17712\/nsj.2021.2.20200145","article-title":"The Non-Syndromic Clinical Spectrums of mtDNA 3243A>G Mutation","volume":"26","author":"Shen","year":"2021","journal-title":"Neurosciences"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ding, Y., Gao, B., and Huang, J. (2022). Mitochondrial Cardiomyopathy: The Roles of Mt-tRNA Mutations. J. Clin. Med., 11.","DOI":"10.3390\/jcm11216431"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1261\/rna.080257.124","article-title":"Mitochondrial tRNA Modifications: Functions, Diseases Caused by Their Loss, and Treatment Strategies","volume":"31","author":"Chujo","year":"2025","journal-title":"RNA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rahmadanthi, F.R., and Maksum, I.P. (2023). Transfer RNA Mutation Associated with Type 2 Diabetes Mellitus. Biology, 12.","DOI":"10.3390\/biology12060871"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/mus.20917","article-title":"Human Mitochondrial Transfer RNAs: Role of Pathogenic Mutation in Disease","volume":"37","author":"Scaglia","year":"2008","journal-title":"Muscle Nerve"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0005-2728(98)00161-3","article-title":"The Mitochondrial Genome: Structure, Transcription, Translation and Replication","volume":"1410","author":"Taanman","year":"1999","journal-title":"Biochim. Et Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.clim.2008.07.011","article-title":"Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus","volume":"129","author":"Vyshkina","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1089\/ars.2013.5702","article-title":"Increased mitochondrial electron transport chain activity at complex I is regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus erythematosus","volume":"21","author":"Doherty","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1002\/art.39791","article-title":"Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus-Prone Mice","volume":"68","author":"Oaks","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial Diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shaukat, A.-N., Kaliatsi, E.G., Stamatopoulou, V., and Stathopoulos, C. (2021). Mitochondrial tRNA-Derived Fragments and Their Contribution to Gene Expression Regulation. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.729452"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.semcdb.2023.06.003","article-title":"Anticodon Stem-Loop tRNA Modifications Influence Codon Decoding and Frame Maintenance during Translation","volume":"154","author":"Smith","year":"2024","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1007\/s11011-021-00772-x","article-title":"Clinical Features, Pathogenesis, and Management of Stroke-like Episodes Due to MELAS","volume":"36","author":"Tetsuka","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ajhg.2008.07.004","article-title":"Pathogenic Mitochondrial DNA Mutations Are Common in the General Population","volume":"83","author":"Elliott","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1093\/eurheartj\/ehv306","article-title":"Sudden Adult Death Syndrome in m.3243A>G-Related Mitochondrial Disease: An Unrecognized Clinical Entity in Young, Asymptomatic Adults","volume":"37","author":"Ng","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1261\/rna.7143305","article-title":"Structural Probing of a Pathogenic tRNA Dimer","volume":"11","author":"Roy","year":"2005","journal-title":"RNA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1016\/S0140-6736(18)30727-X","article-title":"Mitochondrial Medicine in the Omics Era","volume":"391","author":"Rahman","year":"2018","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1056\/NEJMra022567","article-title":"Mitochondrial Respiratory-Chain Diseases","volume":"348","author":"DiMauro","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/348651a0","article-title":"A Mutation in the tRNALeu(UUR) Gene Associated with the MELAS Subgroup of Mitochondrial Encephalomyopathies","volume":"348","author":"Goto","year":"1990","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nusir, A., Sinclair, P., and Kabbani, N. (2023). Mitochondrial Proteomes in Neural Cells: A Systematic Review. Biomolecules, 13.","DOI":"10.3390\/biom13111638"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Na, J.-H., and Lee, Y.-M. (2024). Diagnosis and Management of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes Syndrome. Biomolecules, 14.","DOI":"10.3390\/biom14121524"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1056\/NEJM198905183202001","article-title":"Mitochondrial DNA Deletions in Progressive External Ophthalmoplegia and Kearns-Sayre Syndrome","volume":"320","author":"Moraes","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/s10038-025-01381-7","article-title":"A Novel m.14677 T > C Variant in Mitochondrial tRNAGlu Gene Causes Chronic Progressive External Ophthalmoplegia","volume":"70","author":"Ueda","year":"2025","journal-title":"J. Hum. Genet."},{"key":"ref_34","unstructured":"Shemesh, A., and Margolin, E. (2025). Kearns-Sayre Syndrome. StatPearls [Internet], StatPearls."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0960-8966(02)00283-3","article-title":"A Novel Mitochondrial tRNALeu(UUR) Mutation in a Patient with Features of MERRF and Kearns\u2013Sayre Syndrome","volume":"13","author":"Nishigaki","year":"2003","journal-title":"Neuromuscul. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e18634","DOI":"10.1097\/MD.0000000000018634","article-title":"A Meta-Analysis and Systematic Review of Leigh Syndrome: Clinical Manifestations, Respiratory Chain Enzyme Complex Deficiency, and Gene Mutations","volume":"99","author":"Chang","year":"2020","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1177\/088307380001501109","article-title":"G8363A Mutation in the Mitochondrial DNA Transfer Ribonucleic acidLys Gene: Another Cause of Leigh Syndrome","volume":"15","author":"Shtilbans","year":"2000","journal-title":"J. Child Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"38","DOI":"10.4161\/rna.4.1.4548","article-title":"Mitochondrial tRNA Mutations: Clinical and Functional Perturbations","volume":"4","author":"Zifa","year":"2007","journal-title":"RNA Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1001\/archneur.58.7.1113","article-title":"A New Mitochondrial Point Mutation in the Transfer RNALeu Gene in a Patient With a Clinical Phenotype Resembling Kearns-Sayre Syndrome","volume":"58","author":"Seneca","year":"2001","journal-title":"Arch. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.mito.2011.09.006","article-title":"Leigh Syndrome Caused by a Novel m.4296G>A Mutation in Mitochondrial tRNA Isoleucine","volume":"12","author":"Cox","year":"2012","journal-title":"Mitochondrion"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/NEN.0000000000000195","article-title":"Leigh Syndrome","volume":"74","author":"Lake","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1212\/WNL.49.2.589","article-title":"A Mitochondrial DNA tRNA Val Point Mutation Associated with Adult-Onset Leigh Syndrome","volume":"49","author":"Chalmers","year":"1997","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1007\/s00415-009-5023-8","article-title":"Heteroplasmic Mutation in the Anticodon-Stem of Mitochondrial tRNAVal Causing MNGIE-like Gastrointestinal Dysmotility and Cachexia","volume":"256","author":"Bender","year":"2009","journal-title":"J. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.mito.2011.04.003","article-title":"Mutation in the Mitochondrial tRNAVal Causes Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like Episodes","volume":"11","author":"Glatz","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pacitti, D., Levene, M., Garone, C., Nirmalananthan, N., and Bax, B.E. (2018). Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00669"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1042\/bj20030222","article-title":"Decreased Mitochondrial tRNALys Steady-State Levels and Aminoacylation Are Associated with the Pathogenic G8313A Mitochondrial DNA Mutation","volume":"374","author":"Bacman","year":"2003","journal-title":"Biochem J"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/0022-2828(92)93381-S","article-title":"Ultrastructural Quantitation of Mitochondria and Myofilaments in Cardiac Muscle from 10 Different Animal Species Including Man","volume":"24","author":"Barth","year":"1992","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/eurheartj\/ehm342","article-title":"Classification of the Cardiomyopathies: A Position Statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"29","author":"Elliott","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/01.CIR.93.5.841","article-title":"Report of the 1995 World Health Organization\/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies","volume":"93","author":"Richardson","year":"1996","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.bbrc.2015.01.157","article-title":"Early Onset Cardiomyopathy Associated with the Mitochondrial tRNALeu(UUR) 3271T>C MELAS Mutation","volume":"458","author":"Brisca","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jelectrocard.2006.11.008","article-title":"Complete Heart Block Associated with Noncompaction, Nail-Patella Syndrome, and Mitochondrial Myopathy","volume":"40","author":"Finsterer","year":"2007","journal-title":"J. Electrocardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1253\/circj.66.1045","article-title":"Inhibition of Angiotensin-Converting Enzyme Reduces Susceptibility of Hypertrophied Rat Myocardium to Ventricular Fibrillation","volume":"66","author":"Shimada","year":"2002","journal-title":"Circ. J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Campbell, T., Slone, J., and Huang, T. (2022). Mitochondrial Genome Variants as a Cause of Mitochondrial Cardiomyopathy. Cells, 11.","DOI":"10.3390\/cells11182835"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/S0002-9440(10)65738-0","article-title":"Mitochondrial DNA Mutations and Mitochondrial Abnormalities in Dilated Cardiomyopathy","volume":"153","author":"Arbustini","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7888334","DOI":"10.1155\/humu\/7888334","article-title":"Dilated Cardiomyopathy May Be Associated with a Novel Mitochondrial tRNASer(AGY) Mutation","volume":"2025","author":"Ding","year":"2025","journal-title":"Hum. Mutat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/sj.ejhg.5200622","article-title":"The Mitochondrial DNA Mutation T12297C Affects a Highly Conserved Nucleotide of tRNALeu(CUN) and Is Associated with Dilated Cardiomyopathy","volume":"9","author":"Grasso","year":"2001","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ijcard.2008.04.089","article-title":"Manifestations of the Mitochondrial A3243G Mutation","volume":"137","author":"Finsterer","year":"2009","journal-title":"Int. J. Cardiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0025-7125(05)70568-X","article-title":"Epidemiology and Prevention of Hypertension","volume":"81","author":"He","year":"1997","journal-title":"Med. Clin. North Am."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S0895-7061(99)00252-6","article-title":"Risk Stratification in Hypertension: New Insights from the Framingham Study*1","volume":"13","author":"Kannel","year":"2000","journal-title":"Am. J. Hypertens."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.biocel.2016.07.018","article-title":"The Mitochondrial Calcium Uniporter Is Involved in Mitochondrial Calcium Cycle Dysfunction: Underlying Mechanism of Hypertension Associated with Mitochondrial tRNA Ile A4263G Mutation","volume":"78","author":"Chen","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1080\/10641963.2017.1411497","article-title":"Mitochondrial tRNA Ala C5601T Mutation May Modulate the Clinical Expression of tRNA Met A4435G Mutation in a Han Chinese Family with Hypertension","volume":"40","author":"Zheng","year":"2018","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.3892\/mmr.2017.6216","article-title":"Molecular Characterization of Mitochondrial transferRNAGln and transferRNAMet A4401G Mutations in a Chinese Family with Hypertension","volume":"15","author":"Yu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s11845-019-02143-z","article-title":"Mitochondrial tRNASer(UCN) 7471delC May Be a Novel Mutation Associated with Maternally Transmitted Hypertension","volume":"189","author":"Yang","year":"2020","journal-title":"Ir. J. Med. Sci. (1971-)"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/1873-3468.14049","article-title":"The Molecular Pathology of Pathogenic Mitochondrial tRNA Variants","volume":"595","author":"Richter","year":"2021","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000547311","article-title":"Molecular Characterization of Two Hypertension Pedigrees Carrying Mitochondrial tRNAGln 4386T>C Mutation","volume":"90","author":"Luo","year":"2025","journal-title":"Hum. Hered."},{"key":"ref_66","first-page":"13","article-title":"Maternally Inherited Essential Hypertension May Be Associated with the Mutations in Mitochondrial tRNAGlu Gene","volume":"17","author":"Wang","year":"2024","journal-title":"Pharmacogenomics Pers. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1102521","article-title":"A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA","volume":"306","author":"Wilson","year":"2004","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1093\/nar\/gky1241","article-title":"A Coronary Artery Disease-Associated tRNAThr Mutation Altered Mitochondrial Function, Apoptosis and Angiogenesis","volume":"47","author":"Jia","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e000437","DOI":"10.1161\/JAHA.113.000437","article-title":"Mitochondrial tRNA Variants in Chinese Subjects With Coronary Heart Disease","volume":"3","author":"Qin","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_70","first-page":"1379","article-title":"Mutation Analysis of the Mitochondrial tRNA Genes in Iranian Coronary Atherosclerosis Patients","volume":"46","author":"Heidari","year":"2017","journal-title":"Iran. J. Public Health"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e925401-1","DOI":"10.12659\/MSM.925401","article-title":"Detecting Rare Variants and Heteroplasmy of Mitochondrial DNA from High-Throughput Sequencing in Patients with Coronary Artery Disease","volume":"26","author":"Jia","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e000757","DOI":"10.1161\/JAHA.113.000757","article-title":"tURn the Lights on: Mitochondrial Transport--RNAs and Cardiovascular Disease","volume":"3","author":"Schiattarella","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1016\/S0140-6736(00)03408-5","article-title":"Increased Risk of Stroke in Patients with the A12308G Polymorphism in Mitochondria","volume":"356","author":"Pulkes","year":"2000","journal-title":"Lancet"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.nmd.2023.11.001","article-title":"A New Family with a Case of Severe Early-Onset Muscle Fatigue and a Peculiar Maternally Inherited Painful Swelling in Chewing Muscles Associated with Homoplasmic m.15992A>T Mutation in Mitochondrial tRNAPro","volume":"33","author":"Ghirigato","year":"2023","journal-title":"Neuromuscul. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s100480050063","article-title":"Two Novel Point Mutations of Mitochondrial tRNA Genes in Histologically Confirmed Parkinson Disease","volume":"2","author":"Sprinzl","year":"1999","journal-title":"Neurogenetics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3109\/19401736.2012.717933","article-title":"A new duplication in the mitochondrially encoded tRNA proline gene in a patient with dilated cardiomyopathy","volume":"24","author":"Cardena","year":"2013","journal-title":"Mitochondrial DNA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/pr.2012.43","article-title":"Fatal Neonatal Lactic Acidosis Caused by a Novel de Novo Mitochondrial G7453A tRNA-Serine (UCN) Mutation","volume":"72","author":"Isohanni","year":"2012","journal-title":"Pediatr. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2020.11.015","article-title":"A Mitochondrial Myopathy-Associated tRNASer(UCN) 7453G>A Mutation Alters tRNA Metabolism and Mitochondrial Function","volume":"57","author":"Lin","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e23300","DOI":"10.1016\/j.heliyon.2023.e23300","article-title":"Weaning Difficulty after Severe Pneumonia in Adult-Onset Mitochondrial Myopathy with A3243G Mutation in the Mitochondrial tRNA Gene: A Case Report","volume":"9","author":"Peng","year":"2023","journal-title":"Heliyon"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13038","DOI":"10.1111\/bpa.13038","article-title":"Expression Pattern of Mitochondrial Respiratory Chain Enzymes in Skeletal Muscle of Patients with Mitochondrial Myopathy Associated with the Homoplasmic m.14674T>C Variant","volume":"32","author":"Roos","year":"2022","journal-title":"Brain Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"167043","DOI":"10.1016\/j.bbadis.2024.167043","article-title":"MT-TN Mutations Lead to Progressive Mitochondrial Encephalopathy and Promotes Mitophagy","volume":"1870","author":"Duan","year":"2024","journal-title":"Biochim. Et Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Borgione, E., Lo Giudice, M., Santa Paola, S., Giuliano, M., Di Blasi, F.D., Di Stefano, V., Lupica, A., Brighina, F., Pettinato, R., and Romano, C. (2023). The Mitochondrial tRNASer(UCN) Gene: A Novel m.7484A>G Mutation Associated with Mitochondrial Encephalomyopathy and Literature Review. Life, 13.","DOI":"10.3390\/life13020554"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1007\/s12031-023-02154-7","article-title":"Assessment of tRNAThr and tRNAGln Variants and Mitochondrial Functionality in Parkinson\u2019s Disease (PD) Patients of Tamil Nadu Population","volume":"73","author":"Venkatesan","year":"2023","journal-title":"J. Mol. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1080\/23802359.2020.1839364","article-title":"The Roles of Mitochondrial tRNA Mutations in Non-Dystrophic Myotonias","volume":"5","author":"Yu","year":"2020","journal-title":"Mitochondrial DNA Part B"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000064955","article-title":"Mitochondrial DNA A4336G Mutation in Alzheimer\u2019s and Parkinson\u2019s Diseases","volume":"48","author":"Mir","year":"2002","journal-title":"Eur. Neurol."},{"key":"ref_86","first-page":"111","article-title":"Mitochondrial tRNA(Gln) and tRNA(Thr) gene variants in Parkinson\u2019s disease","volume":"2","author":"Henneberg","year":"1997","journal-title":"Eur. J. Med. Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Buneeva, O., Fedchenko, V., Kopylov, A., and Medvedev, A. (2020). Mitochondrial Dysfunction in Parkinson\u2019s Disease: Focus on Mitochondrial DNA. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120591"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s10038-024-01254-5","article-title":"A Novel Pathogenic Mitochondrial DNA Variant m.4344T>C in tRNAGln Causes Developmental Delay","volume":"69","author":"Yin","year":"2024","journal-title":"J. Hum. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41392-023-01519-z","article-title":"Epigenetic Regulation in Major Depression and Other Stress-Related Disorders: Molecular Mechanisms, Clinical Relevance and Therapeutic Potential","volume":"8","author":"Yuan","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jad.2018.02.012","article-title":"Generalized Anxiety Disorder in Urban China: Prevalence, Awareness, and Disease Burden","volume":"234","author":"Yu","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/humu.21575","article-title":"A Comparative Analysis Approach to Determining the Pathogenicity of Mitochondrial tRNA Mutations","volume":"32","author":"Yarham","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e27041","DOI":"10.1016\/j.heliyon.2024.e27041","article-title":"Mitochondrial tRNASer(UCN) Mutations Associated Non-Syndromic Sensorineural Hearing Loss in Chinese Families","volume":"10","author":"Zhang","year":"2024","journal-title":"Heliyon"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.mito.2012.04.001","article-title":"Mitochondrial tRNA Mutations Associated with Deafness","volume":"12","author":"Zheng","year":"2012","journal-title":"Mitochondrion"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1399-0004.2007.00925.x","article-title":"Haplogroup Analysis Supports a Pathogenic Role for the 7510T>C Mutation of Mitochondrial tRNA Ser(UCN) in Sensorineural Hearing Loss","volume":"73","author":"Labay","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"107235","DOI":"10.1016\/j.jbc.2024.107235","article-title":"Deafness-Associated tRNAPhe Mutation Impaired Mitochondrial and Cellular Integrity","volume":"300","author":"Chen","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9453","DOI":"10.1093\/nar\/gkac720","article-title":"A Deafness-Associated Mitochondrial DNA Mutation Caused Pleiotropic Effects on DNA Replication and tRNA Metabolism","volume":"50","author":"Meng","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e24298","DOI":"10.1002\/jcla.24298","article-title":"Maternally Transmitted Nonsyndromic Hearing Impairment May Be Associated with Mitochondrial tRNAAla 5601C>T and tRNA Leu(CUN) 12311T>C Mutations","volume":"36","author":"Yu","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mutai, H., Watabe, T., Kosaki, K., Ogawa, K., and Matsunaga, T. (2017). Mitochondrial Mutations in Maternally Inherited Hearing Loss. BMC Med. Genet., 18.","DOI":"10.1186\/s12881-017-0389-4"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhou, L., Chan, J.C.Y., Chupin, S., Gueguen, N., Desquiret-Dumas, V., Koh, S.K., Li, J., Gao, Y., Deng, L., and Verma, C. (2020). Increased Protein S-Glutathionylation in Leber\u2019s Hereditary Optic Neuropathy (LHON). Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21083027"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2401856","DOI":"10.1002\/advs.202401856","article-title":"Mitochondrial tRNAGlu 14693A > G Mutation, an \u201cEnhancer\u201d to the Phenotypic Expression of Leber\u2019s Hereditary Optic Neuropathy","volume":"11","author":"Jin","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/cge.14189","article-title":"Toxic and nutritional factors trigger Leber hereditary optic neuropathy due to a mitochondrial tRNA mutation","volume":"102","author":"Emperador","year":"2022","journal-title":"Clinal Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1001\/jama.2025.1597","article-title":"Cataracts: A Review","volume":"333","author":"Chen","year":"2025","journal-title":"JAMA"},{"key":"ref_103","first-page":"143","article-title":"Mitochondrial tRNA-Serine (AGY) m.C12264T Mutation Causes Severe Multisystem Disease with Cataracts","volume":"13","author":"Schrier","year":"2012","journal-title":"Discov. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/ejhg.2012.44","article-title":"Mutations in the Mitochondrial tRNASer(AGY) Gene Are Associated with Deafness, Retinal Degeneration, Myopathy and Epilepsy","volume":"20","author":"Tuppen","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00467-011-1926-6","article-title":"Renal Involvement in Mitochondrial Cytopathies","volume":"27","author":"Emma","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"20","DOI":"10.5414\/CNCS109083","article-title":"Focal Segmental Glomerulosclerosis Associated with Mitochondrial Disease","volume":"5","author":"Lim","year":"2017","journal-title":"Clin. Nephrol.\u2013Case Stud."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrneph.2015.214","article-title":"Mitochondrial Dysfunction in Inherited Renal Disease and Acute Kidney Injury","volume":"12","author":"Emma","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e157418","DOI":"10.1172\/jci.insight.157418","article-title":"Heteroplasmic and Homoplasmic m.616T>C in Mitochondria tRNAPhe Promote Isolated Chronic Kidney Disease and Hyperuricemia","volume":"7","author":"Xu","year":"2022","journal-title":"JCI Insight"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ding, X., Fang, T., Pang, X., Pan, X., Tong, A., Lin, Z., Zheng, S., and Zheng, N. (2023). Mitochondrial DNA Abnormalities and Metabolic Syndrome. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1153174"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0925-4439(95)00036-4","article-title":"Mitochondrial Diabetes Mellitus: A Review","volume":"1271","author":"Gerbitz","year":"1995","journal-title":"Biochim. Et Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e8458","DOI":"10.1002\/ccr3.8458","article-title":"The Clinical and Genetic Characteristics of Maternally Inherited Diabetes and Deafness (MIDD) with Mitochondrial m3243A > G Mutation: A 10-year Follow-up Observation Study and Literature Review","volume":"12","author":"Zheng","year":"2024","journal-title":"Clin. Case Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2057187","DOI":"10.1155\/2020\/2057187","article-title":"Maternally Inherited Diabetes Mellitus Associated with a Novel m.15897G>A Mutation in Mitochondrial tRNA Thr Gene","volume":"2020","author":"Li","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e70056","DOI":"10.1002\/jcla.70056","article-title":"Mitochondrial tRNA Glu 14687A >G May Be A Novel Mutation for Type 2 Diabetes Mellitus","volume":"39","author":"Rao","year":"2025","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0168-8227(99)00138-2","article-title":"Mitochondrial Gene Mutations in Gestational Diabetes Mellitus","volume":"48","author":"Chen","year":"2000","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.3892\/mmr.2016.4916","article-title":"Point Mutation in Mitochondrial tRNA Gene Is Associated with Polycystic Ovary Syndrome and Insulin Resistance","volume":"13","author":"Ding","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12958-024-01337-0","article-title":"Oxidative Stress and Energy Metabolism Abnormalities in Polycystic Ovary Syndrome: From Mechanisms to Therapeutic Strategies","volume":"22","author":"Yan","year":"2024","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Nawaz, T., Awan, T., Zahoor, H., Gul, R., Bibi, S., Uddin, A., Abbas, G., Ghafoor, S.U., Belay, S.A., and Rehman, A. (2025). Analysis of Mutations in Mitochondrial Transfer RNA Genes and the Maternal Inheritance of Polycystic Ovary Syndrome. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1509791"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Kobayashi, H., Matsubara, S., Yoshimoto, C., Shigetomi, H., and Imanaka, S. (2025). A Comprehensive Review of the Contribution of Mitochondrial DNA Mutations and Dysfunction in Polycystic Ovary Syndrome, Supported by Secondary Database Analysis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031172"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mito.2009.01.006","article-title":"Two Novel Cosegregating Mutations in tRNAMet and COX III, in a Patient with Exercise Intolerance and Autoimmune Polyendocrinopathy","volume":"9","author":"Bortot","year":"2009","journal-title":"Mitochondrion"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1182\/blood-2003-07-2446","article-title":"Ineffective Hematopoiesis Linked with a Mitochondrial tRNA Mutation (G3242A) in a Patient with Myelodysplastic Syndrome","volume":"103","author":"Gattermann","year":"2004","journal-title":"Blood"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000542357","article-title":"Screening for Mitochondrial tRNA Variants in 200 Patients with Systemic Lupus Erythematosus","volume":"89","author":"Xuan","year":"2024","journal-title":"Hum. Hered."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"BSR20201856","DOI":"10.1042\/BSR20201856","article-title":"Mitochondrial tRNA Mutations in Chinese Children with Tic Disorders","volume":"40","author":"Jiang","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Wen, Y., and Yao, Y. (2021). Autism Spectrum Disorders: The Mitochondria Connection. Autism Spectrum Disorders, Exon Publications.","DOI":"10.36255\/exonpublications.autismspectrumdisorders.2021.mitochondria"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41380-024-02725-z","article-title":"The Multifaceted Role of Mitochondria in Autism Spectrum Disorder","volume":"30","author":"Khaliulin","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jns.2009.01.025","article-title":"Mitochondrial DNA G8363A Mutation in the tRNALys Gene: Clinical, Biochemical and Pathological Study","volume":"281","author":"Virgilio","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/mp.2010.136","article-title":"Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis","volume":"17","author":"Rossignol","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101895","DOI":"10.1016\/j.genrep.2024.101895","article-title":"Mutational Landscape of Mitochondrial Cytochrome b and Its Flanking tRNA Genes Associated with Increased Mitochondrial DNA Copy Number and Disease Risk in Children with Autism","volume":"35","author":"Adiba","year":"2024","journal-title":"Gene Rep."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Weissman, J.R., Kelley, R.I., Bauman, M.L., Cohen, B.H., Murray, K.F., Mitchell, R.L., Kern, R.L., and Natowicz, M.R. (2008). Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003815"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"133","DOI":"10.31557\/apjcb.2021.6.2.133-139","article-title":"High Prevalence of Mitochondrial tRNA A3243G Mutation in Invasive Breast Cancer","volume":"6","author":"Alhomidi","year":"2021","journal-title":"Asian Pac. J. Cancer Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/humu.22358","article-title":"Pathogenic Mitochondrial t RNA Point Mutations: Nine Novel Mutations Affirm Their Importance as a Cause of Mitochondrial Disease","volume":"34","author":"Blakely","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1038\/s41467-018-06471-z","article-title":"RNA Modification Landscape of the Human Mitochondrial tRNALys Regulates Protein Synthesis","volume":"9","author":"Richter","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2478\/bjmg-2022-0020","article-title":"Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer","volume":"25","author":"Ding","year":"2023","journal-title":"Balk. J. Med. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"367","DOI":"10.21037\/tp-24-462","article-title":"A Rare de Novo Mutation, m.1630A>G, in the Mitochondrial tRNAVal (MT-TV) Gene in a Child with Epilepsy: Case Report and Review of the Literature","volume":"14","author":"Wang","year":"2025","journal-title":"Transl. Pediatr."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ejhg.2011.238","article-title":"The Novel Mitochondrial tRNAAsn Gene Mutation m.5709T>C Produces Ophthalmoparesis and Respiratory Impairment","volume":"20","author":"Ronchi","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1186\/s12967-024-05574-0","article-title":"Queuine Ameliorates Impaired Mitochondrial Function Caused by Mt-tRNAAsn Variants","volume":"22","author":"Lin","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Kusmirek, W., Strozynska, N., Cerpa, P.M.-A., Dziergowska, A., Leszczynska, G., Nowak, R., and Adamczyk, M. (2024). Direct RNA Oxford Nanopore Sequencing Distinguishes between Modifications in tRNA at the U34 Position. bioRxiv, bioRxiv:2024.12.30.630739.","DOI":"10.1101\/2024.12.30.630739"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1016\/j.febslet.2014.09.025","article-title":"A-to-I Editing on tRNAs: Biochemical, Biological and Evolutionary Implications","volume":"588","author":"Torres","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1093\/nar\/gkab104","article-title":"The Human tRNA Taurine Modification Enzyme GTPBP3 Is an Active GTPase Linked to Mitochondrial Diseases","volume":"49","author":"Peng","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7563","DOI":"10.1093\/nar\/gkad139","article-title":"Restoration of Mitochondrial Function through Activation of Hypomodified tRNAs with Pathogenic Mutations Associated with Mitochondrial Diseases","volume":"51","author":"Tomoda","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Magistrati, M., Gilea, A.I., Ceccatelli Berti, C., Baruffini, E., and Dallabona, C. (2023). Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032178"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ajhg.2009.08.004","article-title":"Acute Infantile Liver Failure Due to Mutations in the TRMU Gene","volume":"85","author":"Zeharia","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1093\/nar\/gkad1197","article-title":"Pathological Mutations Promote Proteolysis of Mitochondrial tRNA-Specific 2-Thiouridylase 1 (MTU1) via Mitochondrial Caseinolytic Peptidase (CLPP)","volume":"52","author":"Ahmad","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"100314","DOI":"10.1016\/j.gim.2022.09.015","article-title":"Genotypic and Phenotypic Spectrum of Infantile Liver Failure Due to Pathogenic TRMU Variants","volume":"25","author":"Vogel","year":"2023","journal-title":"Genet. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"7480","DOI":"10.1093\/nar\/gkad591","article-title":"Mitochondrial Haplotype Mutation Alleviates Respiratory Defect of MELAS by Restoring Taurine Modification in tRNA with 3243A > G Mutation","volume":"51","author":"Ueda","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/emmm.201303198","article-title":"The Isolated Carboxy--terminal Domain of Human Mitochondrial leucyl--tRNA Synthetase Rescues the Pathological Phenotype of Mitochondrial tRNA Mutations in Human Cells","volume":"6","author":"Perli","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1074\/jbc.M409306200","article-title":"Mitochondria-Specific RNA-Modifying Enzymes Responsible for the Biosynthesis of the Wobble Base in Mitochondrial tRNAs: Implications for the Molecular Pathogenesis of Human Mitochondrial Diseases","volume":"280","author":"Umeda","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_147","first-page":"1127","article-title":"[Taurine for Mitochondrial Diseases]","volume":"76","author":"Sunada","year":"2024","journal-title":"Brain Nerve"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1136\/jnnp-2018-317964","article-title":"Taurine Supplementation for Prevention of Stroke-like Episodes in MELAS: A Multicentre, Open-Label, 52-Week Phase III Trial","volume":"90","author":"Ohsawa","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/s12276-023-00973-7","article-title":"Trends and Prospects in Mitochondrial Genome Editing","volume":"55","author":"Phan","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5483\/BMBRep.2023-0224","article-title":"Mitochondrial Genome Editing: Strategies, Challenges, and Applications","volume":"57","author":"Lim","year":"2024","journal-title":"BMB Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.omtn.2022.04.033","article-title":"Efficient Suppression of Endogenous CFTR Nonsense Mutations Using Anticodon-Engineered Transfer RNAs","volume":"28","author":"Ko","year":"2022","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Awawdeh, A., Radecki, A.A., and Vargas-Rodriguez, O. (2024). Suppressor tRNAs at the Interface of Genetic Code Expansion and Medicine. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1420331"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Weiss, J.L., Decker, J.C., Bolano, A., and Krahn, N. (2024). Tuning tRNAs for Improved Translation. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1436860"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41573-023-00829-9","article-title":"tRNA Therapeutics for Genetic Diseases","volume":"23","author":"Coller","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/nar\/25.5.955","article-title":"tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence","volume":"25","author":"Lowe","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"9077","DOI":"10.1093\/nar\/gkab688","article-title":"tRNAscan-SE 2.0: Improved Detection and Functional Classification of Transfer RNA Genes","volume":"49","author":"Chan","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.molmed.2020.02.006","article-title":"Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective","volume":"26","author":"Jackson","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"101437","DOI":"10.1016\/j.gendis.2024.101437","article-title":"Mitochondrial DNA Editing: Key to the Treatment of Neurodegenerative Diseases","volume":"12","author":"Hong","year":"2025","journal-title":"Genes Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12023\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:43:13Z","timestamp":1765791793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":158,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412023"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412023","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]}}}