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DOI | 10.1038/nature24285 |
Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis | |
Wong, Yvette C.; Ysselstein, Daniel; Krainc, Dimitri | |
2018-02-15 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2018 |
卷号 | 554期号:7692页码:382-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Both mitochondria and lysosomes are essential for maintaining cellular homeostasis, and dysfunction of both organelles has been observed in multiple diseases(1-4). Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network, which drives cellular metabolism(5). Lysosomes similarly undergo constant dynamic regulation by the RAB7 GTPase(1), which cycles from an active GTP-bound state into an inactive GDP-bound state upon GTP hydrolysis. Here we have identified the formation and regulation of mitochondrialysosome membrane contact sites using electron microscopy, structured illumination microscopy and high spatial and temporal resolution confocal live cell imaging. Mitochondria-lysosome contacts formed dynamically in healthy untreated cells and were distinct from damaged mitochondria that were targeted into lysosomes for degradation(6,7). Contact formation was promoted by active GTP-bound lysosomal RAB7, and contact untethering was mediated by recruitment of the RAB7 GTPase-activating protein TBC1D15 to mitochondria by FIS1 to drive RAB7 GTP hydrolysis and thereby release contacts. Functionally, lysosomal contacts mark sites of mitochondrial fission, allowing regulation of mitochondrial networks by lysosomes, whereas conversely, mitochondrial contacts regulate lysosomal RAB7 hydrolysis via TBC1D15. Mitochondrialysosome contacts thus allow bidirectional regulation of mitochondrial and lysosomal dynamics, and may explain the dysfunction observed in both organelles in various human diseases. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000424996300043 |
WOS关键词 | PARKINSONS-DISEASE ; SITES ; ER ; PROTEINS ; DIVISION ; ACTIN ; NEURODEGENERATION ; DYSFUNCTION ; ORGANELLES ; DYNAMICS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202800 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA |
推荐引用方式 GB/T 7714 | Wong, Yvette C.,Ysselstein, Daniel,Krainc, Dimitri. Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis[J]. NATURE,2018,554(7692):382-+. |
APA | Wong, Yvette C.,Ysselstein, Daniel,&Krainc, Dimitri.(2018).Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis.NATURE,554(7692),382-+. |
MLA | Wong, Yvette C.,et al."Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis".NATURE 554.7692(2018):382-+. |
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