ArticleScience advances2022
Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms.
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Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed.
- Article
- Cis-3-hexen-1-ol suppresses bladder cancer progression by inducing mitophagy via the PCK2/AMPK/mTOR signaling pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.Journal of diabetes · 2026Review
- Mitochondria-Derived Vesicles and Mitochondrial Extracellular Vesicles in Health and Cardiovascular Disease.Circulation research · 2026Review
- Mitochondrial interplay with membrane organelles in health and disease.Cell communication and signaling : CCS · 2026Review
- A cocktail hydrogel promoting the functional interneurons regeneration of human neural progenitor cells for brain injury therapy.Journal of advanced research · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- Mitochondria beyond boundaries: from cellular powerhouses to intercellular messengers in health and disease.Science China. Life sciences · 2026Review
- Microautophagy: definition, classification, and the complexity of the underlying mechanisms.Autophagy · 2026Review
- Blockade of mitochondrial components release by exosome pathway promotes the pathogenesis of Fuchs endothelial corneal dystrophy.Cell death discovery · 2025Article
- Mapping the global research landscape of mitophagy in Parkinson's disease: a bibliometric and visualization analysis.Hereditas · 2025Article
- Label-free robotic mitochondrial biopsy.Science advances · 2025Article
- MDVs bridge metabolite signals to mitochondrial fitness.Life metabolism · 2025Article
- Neuronal regulated cell death in aging-related neurodegenerative diseases: key pathways and therapeutic potentials.Neural regeneration research · 2025Article
- Mitochondrial Quality Control in Bovine Oocyte Maturation: Mechanisms, Challenges, and Prospects for Enhancing Reproductive Efficiency.Animals : an open access journal from MDPI · 2025Review
- Impaired microglial glycolysis promotes inflammatory responses after intracerebral haemorrhage via HK2-dependent mitochondrial dysfunction.Journal of advanced research · 2025Article
- Super-resolution imaging informed scRNA sequencing analysis reveals the critical role of GDF15 in rejuvenating aged hematopoietic stem cells.Blood science (Baltimore, Md.) · 2025Article
- Pulmonary mitochondrial DNA release and activation of the cGAS-STING pathway in Lethal Stx12 knockout mice.Cell communication and signaling : CCS · 2025Article
- Staphylococcus aureus induces mitophagy via the HDAC11/IL10 pathway to sustain intracellular survival.Journal of translational medicine · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
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Authors and funding
35 authors.
Feixiang BaoCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-6985-2602
Lingyan ZhouCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Rui ZhouDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0001-5373-6917
Qiaoying HuangGuangdong Provincial Key Laboratory of Brain Function and Disease, Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.ORCID 0000-0001-6643-2509
Junguo ChenGuangdong Provincial Key Laboratory of Brain Function and Disease, Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Sheng ZengCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Yi WuCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0001-7247-7404
Liang YangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Shufang QianDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Mengfei WangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Xueying HeCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Shan LiangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Juntao QiCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Ge XiangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Qi LongCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-7003-0104
Jingyi GuoCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Zhongfu YingCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Yanshuang ZhouCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-7009-9769
Qiuge ZhaoThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Jiwei ZhangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.ORCID 0000-0002-3826-7611
Di ZhangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Wei SunCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Mi GaoCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-4085-1374
Hao WuCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-9558-9879
Yifan ZhaoCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Jinfu NieCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Min LiSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Quan ChenCollege of Life Sciences, Nankai University, Tianjin, China.
Jiekai ChenCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0001-5168-7074
Xiao ZhangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-3894-8513
Guangjin PanCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-2378-7198
Hong ZhangDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0002-4084-5150
Mingtao LiGuangdong Provincial Key Laboratory of Brain Function and Disease, Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Mei TianDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0002-1587-2114
Xingguo LiuCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0001-7060-8204
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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