| 論文編號: |
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| 第一作者所在部門: |
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| 中文論文題目: |
Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms |
| 英文論文題目: |
Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms |
| 作者: |
Feixiang Bao; Lingyan Zhou; Rui Zhou; Qiaoying Huang; Junguo Chen; Sheng Zeng; Yi Wu; Liang Yang; Shufang Qian; Mengfei Wang; Xueying He1; Shan Liang; Juntao Qi; Ge Xiang; Qi Long; Jingyi Guo; Zhongfu Ying; Yanshuang Zhou; Qiuge Zhao; Jiwei Zhang; Di Zhang; Wei Sun; Mi Gao; Hao Wu; Yifan Zhao; Jinfu Nie; Min Li; Quan Chen; Jiekai Chen; Xiao Zhang; Guangjin Pan; Hong Zhang; Mingtao Li; Mei Tian; Xingguo Liu |
| 論文出處: |
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| 刊物名稱: |
Science Advances |
| 年: |
2022 |
| 卷: |
8 |
| 期: |
15 |
| 頁: |
2376 |
| 聯係作者: |
Xingguo Liu |
| 收錄類別: |
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| 影響因子: |
14.98 |
| 摘要: |
Mitochondrial quality control plays an important role in maintaining mitochondrial homeostasis and function. Disruption of mitochondrial quality control degrades brain function. We found that flunarizine (FNZ), a drug whose chronic use causes parkinsonism, led to a parkinsonism-like motor dysfunction in mice. FNZ induced mitochondrial dysfunction and decreased mitochondrial mass specifically in the brain. FNZ decreased mitochondrial content in both neurons and astrocytes, without affecting the number of nigral dopaminergic neurons. In human neural progenitor cells, FNZ also induced mitochondrial depletion. Mechanistically, independent of ATG5- or RAB9-mediated mitophagy, mitochondria were engulfed by lysosomes, followed by a vesicle-associated membrane protein 2- and syntaxin-4-dependent extracellular secretion. A genome-wide CRISPR knockout screen identified genes required for FNZ-induced mitochondrial elimination. These results reveal not only a previously unidentified lysosome-associated exocytosis process of mitochondrial quality control that may participate in the FNZ-induced parkinsonism but also a drug-based method for generating mitochondria-depleted mammal cells. |
| 英文摘要: |
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