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Acetylated tau exacerbates apoptosis by disturbing mitochondrial dynamics in HEK293 cells
Authors:Jun-Fei Zhang  Zhi-Ting Fang  Jun-Ning Zhao  Gong-Ping Liu  Xin Shen  Gao-Feng Jiang  Qian Liu
Affiliation:1. Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Contribution: ​Investigation;2. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Contribution: Methodology;3. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Contribution: ​Investigation;4. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China;5. School of Stomatology and Ophthalmology, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, China;6. Center for Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China

Abstract:An increase in tau acetylation at K274 and K281 and abnormal mitochondrial dynamics have been observed in the brains of Alzheimer's disease (AD) patients. Here, we constructed three types of tau plasmids, TauKQ (acetylated tau mutant, by mutating its K274/K281 into glutamine to mimic disease-associated lysine acetylation), TauKR (non-acetylated tau mutant, by mutating its K274/K281 into arginine), and TauWT (wild-type human full-length tau). By transfecting these tau plasmids in HEK293 cells, we found that TauWT and TauKR induced mitochondrial fusion by increasing the level of mitochondrial fusion proteins. Conversely, TauKQ induced mitochondrial fission by reducing mitochondrial fusion proteins, exacerbating mitochondrial dysfunction and apoptosis. BGP-15 ameliorated TauKQ-induced mitochondrial dysfunction and apoptosis by improving mitochondrial dynamics. Our findings suggest that acetylation of K274/281 represents an important post-translational modification site regulating mitochondrial dynamics, and that BGP-15 holds potential as a therapeutic agent for mitochondria-associated diseases such as AD.
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Keywords:acetylation  Alzheimer's disease  apoptosis  mitochondrial dynamics  tau
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