Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice

• 成果类型: Article
• 署名作者: Li, Wenwen; Li, Jiarui; Li, Jing; Wei, Chen; Laviv, Tal; Dong, Meiyi; Lin, Jingran; Calubag, Mariah; Colgan, Lesley A.; Jin, Kai; Zhou, Bing; Shen, Ying; Li, Haohong; Cui, Yihui; Gao, Zhihua; Li, Tao; Hu, Hailan; Yasuda, Ryohei; Ma, Huan
• 署名单位: Zhejiang University; Liangzhu Laboratory; Zhejiang University; Zhejiang University; Zhejiang University; Zhejiang University; Zhejiang University; Tel Aviv University; Tel Aviv University; University of Wisconsin System; University of Wisconsin Madison; US Department of Veterans Affairs; Veterans Health Administration (VHA); William S Middleton Memorial Veterans Hospital; Max Planck Society; Beihang University; Chinese Academy of Medical Sciences - Peking Union Medical College
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10549
• DOI: 10.1126/science.adp6547
• 发表日期: 2024-12-20
• 关键词: element-binding protein; camp-responsive element; dendritic mitochondria; mediated transcription; creb binding; camkii; plasticity; DYNAMICS; nucleus; phosphorylation

摘要

Deciphering the complex interplay between neuronal activity and mitochondrial function is pivotal in understanding brain aging, a multifaceted process marked by declines in synaptic function and mitochondrial performance. Here, we identified an age-dependent coupling between neuronal and synaptic excitation and mitochondrial DNA transcription (E-TCmito), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TCnuc). We demonstrated that E-TCmito repurposes molecules traditionally associated with E-TCnuc to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TCmito weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TCmito in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.