caa a22 4500 606235272 CHVBK 20210128101241.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2493-0 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2493-0 The tRNAGly T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNAGly, increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential [Elektronische Daten] [Wei Li, Chaowei Wen, Weixing Li, Hailing Wang, Xiaomin Guan, Wanlin Zhang, Wei Ye, Jianxin Lu] Mitochondrial diabetes originates mainly from mutations located in maternally transmitted, mitochondrial tRNA-coding genes. In a genetic screening program of type 2 diabetes conducted with a Chinese Han population, we found one family with suggestive maternally transmitted diabetes. The proband's mitochondrial genome was analyzed using DNA sequencing. Total 42 known nucleoside changes and 1 novel variant were identified, and the entire mitochondrial DNA sequence was assigned to haplogroup M11b. Phylogenetic analysis showed that a homoplasmic mutation, 10003T>C transition, occurred at the highly conserved site in the gene encoding tRNAGly. Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNAGly significantly affected andthe amount of tRNAGly decreased by 97%, production of reactive oxygen species was enhanced, and mitochondrial membrane potential, mtDNA copy number and cellular oxygen consumption rate were remarkably decreased compared with wild-type cybrid cells. The homoplasmic 10003T>C mutation in the mitochondrial tRNAGly gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family. Springer Science+Business Media New York, 2015 Mitochondrial diabetes nationallicence Mitochondrial tRNA glycine nationallicence m.10003T>C mutation nationallicence Reactive oxygen species nationallicence Mitochondrial membrane potential nationallicence Li Wei Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut Wen Chaowei Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut Li Weixing Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, 310014, Hangzhou, Zhejiang, People's Republic of China aut Wang Hailing Zhejiang Provincial Key Laboratory of Medical Genetics, 325035, Wenzhou, Zhejiang, People's Republic of China aut Guan Xiaomin Zhejiang Provincial Key Laboratory of Medical Genetics, 325035, Wenzhou, Zhejiang, People's Republic of China aut Zhang Wanlin Zhejiang Provincial Key Laboratory of Medical Genetics, 325035, Wenzhou, Zhejiang, People's Republic of China aut Ye Wei Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut Lu Jianxin Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 171-179 0300-8177 408:1-2<171 2015 408 11010 https://doi.org/10.1007/s11010-015-2493-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2493-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Wei Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Wen Chaowei Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Li Weixing Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, 310014, Hangzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Wang Hailing Zhejiang Provincial Key Laboratory of Medical Genetics, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Guan Xiaomin Zhejiang Provincial Key Laboratory of Medical Genetics, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Wanlin Zhejiang Provincial Key Laboratory of Medical Genetics, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Ye Wei Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Lu Jianxin Key Laboratory of Laboratory Medicine, Ministry of Education, 325035, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 171-179 0300-8177 408:1-2<171 2015 408 11010