翻译(生物学)
生物合成
线粒体
片段(逻辑)
谷氨酸受体
生物
细胞生物学
计算生物学
化学
神经科学
遗传学
基因
信使核糖核酸
计算机科学
受体
程序设计语言
作者
Dingfeng Li,Xinyi Gao,Xiaolin Ma,Ming Wang,Cheng Chen,Tian Xue,Feng Gao,Yong Shen,Juan Zhang,Qiang Liang
标识
DOI:10.1016/j.cmet.2024.02.011
摘要
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.
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