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泛素连接酶 MARCH5 定位于过氧化物酶体以调节过氧化物酶体自噬。

Ubiquitin ligase MARCH5 localizes to peroxisomes to regulate pexophagy.

机构信息

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

出版信息

J Cell Biol. 2022 Jan 3;221(1). doi: 10.1083/jcb.202103156. Epub 2021 Nov 8.

DOI:10.1083/jcb.202103156
PMID:34747980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8579195/
Abstract

Mitochondria and peroxisomes are independent but functionally closely related organelles. A few proteins have been characterized as dual-organelle locating proteins with distinct or similar roles on mitochondria and peroxisomes. MARCH5 is a mitochondria-associated ubiquitin ligase best known for its regulatory role in mitochondria quality control, fission, and fusion. Here, we used a proximity tagging system, PUP-IT, and identified new interacting proteins of MARCH5. Our data uncover that MARCH5 is a dual-organelle locating protein that interacts with several peroxisomal proteins. PEX19 binds the transmembrane region on MARCH5 and targets it to peroxisomes. On peroxisomes, MARCH5 binds and mediates the ubiquitination of PMP70. Furthermore, we find PMP70 ubiquitination and pexophagy induced by mTOR inhibition are blocked in the absence of MARCH5. Our study suggests novel roles of MARCH5 on peroxisomes.

摘要

线粒体和过氧化物酶体是独立但功能上密切相关的细胞器。有一些蛋白质被鉴定为双器官定位蛋白，它们在线粒体和过氧化物酶体上具有不同或相似的作用。MARCH5 是一种与线粒体相关的泛素连接酶，因其在调节线粒体质量控制、分裂和融合方面的作用而广为人知。在这里，我们使用了一种邻近标记系统 PUP-IT，并鉴定了 MARCH5 的新的相互作用蛋白。我们的数据揭示，MARCH5 是一种双器官定位蛋白，与几种过氧化物酶体蛋白相互作用。PEX19 结合 MARCH5 的跨膜区域，并将其靶向过氧化物酶体。在过氧化物酶体上，MARCH5 结合并介导 PMP70 的泛素化。此外，我们发现 mTOR 抑制时诱导的 PMP70 泛素化和过氧化物酶体自噬在没有 MARCH5 的情况下被阻断。我们的研究表明 MARCH5 在过氧化物酶体上具有新的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/67aa7f9e9551/JCB_202103156_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/87010bd94ab5/JCB_202103156_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/8ae76750370c/JCB_202103156_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/6539d031a2b7/JCB_202103156_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/de31c981ddf5/JCB_202103156_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/85415f96d158/JCB_202103156_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/d42c587c026b/JCB_202103156_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/0390d6a1cfef/JCB_202103156_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/4d7665a4f64c/JCB_202103156_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/dde23cff36df/JCB_202103156_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/327b5a7427c2/JCB_202103156_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/d9fc507feebb/JCB_202103156_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/2b352ec5c34e/JCB_202103156_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/65d3edfedfa3/JCB_202103156_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/67aa7f9e9551/JCB_202103156_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/87010bd94ab5/JCB_202103156_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/8ae76750370c/JCB_202103156_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/6539d031a2b7/JCB_202103156_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/de31c981ddf5/JCB_202103156_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/85415f96d158/JCB_202103156_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/d42c587c026b/JCB_202103156_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/0390d6a1cfef/JCB_202103156_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/4d7665a4f64c/JCB_202103156_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/dde23cff36df/JCB_202103156_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/327b5a7427c2/JCB_202103156_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/d9fc507feebb/JCB_202103156_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/2b352ec5c34e/JCB_202103156_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/65d3edfedfa3/JCB_202103156_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7045/8579195/67aa7f9e9551/JCB_202103156_Fig9.jpg

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