Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice
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-TC<sub>mito</sub>), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC<sub>nuc</sub>). We demonstrated that E-TC<sub>mito</sub> repurposes molecules traditionally associated with E-TC<sub>nuc</sub> to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC<sub>mito</sub> weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC<sub>mito</sub> in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.
Authors
- Tal Laviv (ORCID: https://orcid.org/0000-0003-1460-6698)
- Mingyi Dong (ORCID: https://orcid.org/0009-0003-2816-9377)
- Haohong Li (ORCID: https://orcid.org/0000-0002-9676-1001)
- Kai Jin (ORCID: https://orcid.org/0009-0007-7846-6539)
- Jiarui Li (ORCID: https://orcid.org/0009-0002-9714-4846)
- Hailan Hu (ORCID: https://orcid.org/0000-0002-0425-5057)
- Lesley A. Colgan (ORCID: https://orcid.org/0000-0003-2089-6820)
- Jingran Lin
- Ying Shen (ORCID: https://orcid.org/0000-0001-7034-5328)
- Yihui Cui (ORCID: https://orcid.org/0000-0002-7362-6237)
- Mariah F. Calubag (ORCID: https://orcid.org/0000-0003-4843-3668)
- Huan Ma (ORCID: https://orcid.org/0000-0003-4359-8631)
- Ryohei Yasuda (ORCID: https://orcid.org/0000-0001-6263-9297)
- Zhihua Gao (ORCID: https://orcid.org/0000-0001-8603-0777)
- Wenwen Li (ORCID: https://orcid.org/0000-0002-3788-0393)
- Tao Li (ORCID: https://orcid.org/0000-0003-3831-901X)
- Bing Zhou (ORCID: https://orcid.org/0000-0002-7718-2311)
- Wei Chen (ORCID: https://orcid.org/0000-0002-3792-6638)
- Jing Li (ORCID: https://orcid.org/0009-0000-6253-6423)
Institutions
- University of Wisconsin–Madison (US)
- Tel Aviv University (IL)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Max Planck Florida Institute for Neuroscience (US)
- Hangzhou Seventh Peoples Hospital (CN)
- William S. Middleton Memorial Veterans Hospital (US)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University (CN)
- Beihang University (CN)
Publication Details
- Journal
- Science
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1126/science.adp6547
- Citations
- 33
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 7.72