Ding Y, Yu XJ, Guo QX, Leng JH. Functional analysis of the novel mitochondrial tRNATrp and tRNASer(AGY) variants associated with type 2 diabetes mellitus. World J Diabetes 2024; 15(8): 1753-1763 [PMID: 39192858 DOI: 10.4239/wjd.v15.i8.1753]
Corresponding Author of This Article
Yu Ding, MD, Associate Professor, Central Laboratory, Hangzhou First People’s Hospital, No. 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China. dingyu_zj@126.com
Research Domain of This Article
Genetics & Heredity
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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Ding Y, Yu XJ, Guo QX, Leng JH. Functional analysis of the novel mitochondrial tRNATrp and tRNASer(AGY) variants associated with type 2 diabetes mellitus. World J Diabetes 2024; 15(8): 1753-1763 [PMID: 39192858 DOI: 10.4239/wjd.v15.i8.1753]
Author contributions: Ding Y contributed to conceptualization; Ding Y and Yu XJ contributed to formal analysis; Ding Y, Guo QX, and Leng JH contributed to investigation; Ding Y and Yu XJ contributed to writing-original draft preparation; Ding Y contributed to writing-review and editing; and all authors have read and agreed to the published version of the manuscript.
Supported bythe Hangzhou Joint Fund of the Zhejiang Provincial Natural Science Foundation of China, No. LHZY24H020002; Hangzhou Municipal Health Commission, No. ZD20220010; and Quzhou Bureau of Science and Technology, No. 2022K51.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Hangzhou First People’s Hospital (Approval No. KY-20240327-0100-01).
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Data sharing statement: The datasets for this study will be available from the corresponding authors upon reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu Ding, MD, Associate Professor, Central Laboratory, Hangzhou First People’s Hospital, No. 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China. dingyu_zj@126.com
Received: February 15, 2024 Revised: May 9, 2024 Accepted: June 18, 2024 Published online: August 15, 2024 Processing time: 162 Days and 0 Hours
Core Tip
Core Tip: We established cytoplasmic hybrid (cybrid) cells with m.A5514G and m.C12237T variants, and control cells without these variants. The m.A5514G variant decreased mt-tRNATrp stability, whereas the m.C12237T variant did not alter the stability of mt-tRNASer(AGY). More severe mitochondrial dysfunction was observed in mutant cybrids than in control cells, indicating that the m.A5514G variant impaired mt-tRNATrp metabolism and mitochondrial functions and increased cellular oxidative stress, which play central roles in type 2 diabetes mellitus (T2DM) progression. By contrast, the m.C12237T variant acted as a modifier of the m.A5514G variant. Our study provides novel insight into the pathophysiology of maternally transmitted T2DM caused by novel mt-tRNA variants.
