Cell reports · 2024
Pyruvate dehydrogenase complex E1 subunit α crotonylation modulates cocaine-associated memory through hippocampal neuron activation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Li Hongchun, Liuha Xiaoyu, Chen Rong, Xiao Yuzhou, Xu Wei, Zhou Yuanyi, Bai Lin, Zhang Jie, Zhao Yue, Zhao Ying, Wang Liang, Qin Feng, Chen Yaxing, Han Shuang, Wei Qingfan, Li Shu, Zhang Dingwen, Bu Qian, Wang Xiaojie, Jiang Linhong, Dai Yanping, Zhang Ni, Kuang Weihong, Qin Meng, Wang Hongbo, Tian Jingwei, Zhao Yinglan, Cen Xiaobo
Аннотация
Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.