Abstract
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 and the 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.
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Acknowledgments
We would thank Xiaoling Xu, Yi Zheng, Huaibin Zhou, and Hongxiang Xu for their kind assistance in FACS detection, PCR analysis, and cell line construction. This work was supported by the National Natural Science Foundation of China (30900811, 81271918), Zhejiang Provincial Natural Science Foundation of China (Y2090753), Key Science and Technology Innovation Team of Zhejiang Province (2010R50048-1), Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents, Medical Scientific Projects from Health Bureau of Zhejiang Province (2011ZDA016) and Wenzhou Science & Technology Bureau (Y20080120).
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Wei Li and Chaowei Wen have contributed equally to this work.
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Li, W., Wen, C., Li, W. et al. 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. Mol Cell Biochem 408, 171–179 (2015). https://doi.org/10.1007/s11010-015-2493-0
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DOI: https://doi.org/10.1007/s11010-015-2493-0