Acetylated tau exacerbates apoptosis by disturbing mitochondrial dynamics in HEK293 cells

Mitochondrial dynamics include two processes: mitochondrial fission and fusion. TauKQ induced mitochondrial fission by decreasing mitochondrial fusion proteins, which aggravated mitochondrial dysfunction and apoptosis. BGP-15 reversed TauKQ-induced mitochondrial dysfunctions and apoptosis by improving mitochondrial dynamics. AbstractAn 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.

Source: Journal of Neurochemistry - January 26, 2024 Category: Neuroscience Authors: Jun ‐Fei Zhang, Zhi‐Ting Fang, Jun‐Ning Zhao, Gong‐Ping Liu, Xin Shen, Gao‐Feng Jiang, Qian Liu Tags: ORIGINAL ARTICLE Source Type: research