老化诱导的 tRNAGlu 衍生片段通过靶向线粒体翻译依赖性嵴组织来损害谷氨酸的生物合成。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-07 DOI:10.1016/j.cmet.2024.02.011
Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu
{"title":"老化诱导的 tRNAGlu 衍生片段通过靶向线粒体翻译依赖性嵴组织来损害谷氨酸的生物合成。","authors":"Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu","doi":"10.1016/j.cmet.2024.02.011","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNA<sup>Glu</sup> in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNA<sup>Leu</sup> and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNA<sup>Leu</sup> aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.</p>","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Aging-induced tRNA<sup>Glu</sup>-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.\",\"authors\":\"Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu\",\"doi\":\"10.1016/j.cmet.2024.02.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNA<sup>Glu</sup> in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNA<sup>Leu</sup> and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNA<sup>Leu</sup> aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.</p>\",\"PeriodicalId\":93927,\"journal\":{\"name\":\"Cell metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell metabolism\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmet.2024.02.011\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.02.011","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/7 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

线粒体嵴是线粒体内膜的折叠部分,随着年龄的增长,其结构会发生异常变化。然而,其潜在的分子机制及其对大脑衰老的贡献在很大程度上还难以捉摸。在这里,我们观察到谷氨酸能神经元线粒体中Glu-5'tsRNA-CTC(一种转移RNA衍生的小RNA(tsRNA))的积累与年龄有关,这种小RNA来自核编码的tRNAGlu。线粒体 Glu-5'tsRNA-CTC 破坏了 mt-tRNALeu 和亮氨酰-tRNA 合成酶 2(LaRs2)的结合,损害了 mt-tRNALeu 氨基酰化和线粒体编码蛋白质的翻译。线粒体翻译缺陷破坏了嵴的组织,导致谷氨酰胺酶(GLS)依赖性谷氨酸形成受损和突触体谷氨酸水平降低。此外,Glu-5'tsRNA-CTC 的减少能保护老年大脑免受线粒体嵴组织、谷氨酸代谢、突触结构和记忆中与年龄相关的缺陷的影响。因此,除了说明正常线粒体嵴超微结构在维持谷氨酸水平中的生理作用外,我们的研究还确定了 tsRNA 在大脑衰老和与年龄相关的记忆衰退中的病理作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Aging-induced tRNAGlu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.

Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation. Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females. Serine and glycine physiology reversibly modulate retinal and peripheral nerve function. TNF compromises intestinal bile-acid tolerance dictating colitis progression and limited infliximab response. Acetate enables metabolic fitness and cognitive performance during sleep disruption.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1