| First Author | Li D | Year | 2024 |
| Journal | Cell Metab | Volume | 36 |
| Issue | 5 | Pages | 1059-1075.e9 |
| PubMed ID | 38458203 | Mgi Jnum | J:357375 |
| Mgi Id | MGI:7618173 | Doi | 10.1016/j.cmet.2024.02.011 |
| Citation | Li D, et al. (2024) Aging-induced tRNA(Glu)-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization. Cell Metab |
| abstractText | 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(Glu) in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNA(Leu) and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNA(Leu) 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. |
