Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2024; 15(8): 1753-1763
Published online Aug 15, 2024. doi: 10.4239/wjd.v15.i8.1753
Functional analysis of the novel mitochondrial tRNATrp and tRNASer(AGY) variants associated with type 2 diabetes mellitus
Yu Ding, Xue-Jiao Yu, Qin-Xian Guo, Jian-Hang Leng
Yu Ding, Qin-Xian Guo, Jian-Hang Leng, Central Laboratory, Hangzhou First People’s Hospital, Hangzhou 310006, Zhejiang Province, China
Xue-Jiao Yu, Clinical Laboratory, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Co-first authors: Yu Ding and Xue-Jiao Yu.
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 by the 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.