title: The tRNA(Gly) T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNA(Gly), increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential.
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 tRNA(Gly). Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNA(Gly) significantly affected and the amount of tRNA(Gly) 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 tRNA(Gly) gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, 325035, Zhejiang, People's Republic of China.|Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, 325035, Zhejiang, People's Republic of China.|Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Higher Education Park, Chashan Town, Wenzhou, 325035, Zhejiang, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, 325035, Zhejiang, People's Republic of China.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Wen
authors.affiliation: Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, People's Republic of China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, 325035, Zhejiang, People's Republic of China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, 325035, Zhejiang, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Guan
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, 325035, Zhejiang, People's Republic of China.
authors.forename: Wanlin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, 325035, Zhejiang, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, 325035, Zhejiang, People's Republic of China. jxlu313@163.com.|Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, 325035, Zhejiang, People's Republic of China. jxlu313@163.com.|Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Higher Education Park, Chashan Town, Wenzhou, 325035, Zhejiang, People's Republic of China. jxlu313@163.com.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
mesh_terms: D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics*; D009154:Mutation; D010101:Oxygen Consumption; D010375:Pedigree; D010802:Phylogeny; D012353:RNA, Transfer, Gly / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D012353:RNA, Transfer, Gly; D017382:Reactive Oxygen Species
keywords: Mitochondrial diabetes; Mitochondrial membrane potential; Mitochondrial tRNA glycine; Reactive oxygen species; m.10003T>C mutation