TFEB
溶酶体
细胞生物学
星形胶质细胞
生物
神经科学
内分泌学
化学
生物化学
中枢神经系统
酶
作者
Jia‐Wen Mo,Peng‐Li Kong,Li Ding,Jun Fan,Jing Ren,Chenglin Lu,Fang Guo,Liang‐Yu Chen,Ran Mo,Qiuling Zhong,You‐Lu Wen,Tingting Gu,Qian‐Wen Wang,Shuji Li,Ting Guo,Tianming Gao,Xiong Cao
标识
DOI:10.1002/advs.202403389
摘要
Abstract Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome‐related genes revealed that the expression of the mucolipin 1 gene ( Mcoln1 ; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte‐specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive‐like behaviors by inhibiting lysosomal exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive‐like behaviors induced by astrocyte‐specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress‐sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.
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