Suppr超能文献

哺乳动物过氧化物酶体膜上的PEX5和泛素动力学

PEX5 and ubiquitin dynamics on mammalian peroxisome membranes.

作者信息

Brown Aidan I, Kim Peter K, Rutenberg Andrew D

机构信息

Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, Canada.

Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada ; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.

出版信息

PLoS Comput Biol. 2014 Jan;10(1):e1003426. doi: 10.1371/journal.pcbi.1003426. Epub 2014 Jan 16.

Abstract

Peroxisomes are membrane-bound organelles within eukaryotic cells that post-translationally import folded proteins into their matrix. Matrix protein import requires a shuttle receptor protein, usually PEX5, that cycles through docking with the peroxisomal membrane, ubiquitination, and export back into the cytosol followed by deubiquitination. Matrix proteins associate with PEX5 in the cytosol and are translocated into the peroxisome lumen during the PEX5 cycle. This cargo translocation step is not well understood, and its energetics remain controversial. We use stochastic computational models to explore different ways the AAA ATPase driven removal of PEX5 may couple with cargo translocation in peroxisomal importers of mammalian cells. The first model considered is uncoupled, in which translocation is spontaneous, and does not immediately depend on PEX5 removal. The second is directly coupled, in which cargo translocation only occurs when its PEX5 is removed from the peroxisomal membrane. The third, novel, model is cooperatively coupled and requires two PEX5 on a given importomer for cargo translocation--one PEX5 with associated cargo and one with ubiquitin. We measure both the PEX5 and the ubiquitin levels on the peroxisomes as we vary the matrix protein cargo addition rate into the cytosol. We find that both uncoupled and directly coupled translocation behave identically with respect to PEX5 and ubiquitin, and the peroxisomal ubiquitin signal increases as the matrix protein traffic increases. In contrast, cooperatively coupled translocation behaves dramatically differently, with a ubiquitin signal that decreases with increasing matrix protein traffic. Recent work has shown that ubiquitin on mammalian peroxisome membranes can lead to selective degradation by autophagy, or 'pexophagy.' Therefore, the high ubiquitin level for low matrix cargo traffic with cooperatively coupled protein translocation could be used as a disuse signal to mediate pexophagy. This mechanism may be one way that cells could regulate peroxisome numbers.

摘要

过氧化物酶体是真核细胞内的膜结合细胞器,它能在翻译后将折叠好的蛋白质导入其基质。基质蛋白的导入需要一种穿梭受体蛋白,通常是PEX5,它通过与过氧化物酶体膜对接、泛素化,然后输出回到细胞质中,随后进行去泛素化,如此循环。基质蛋白在细胞质中与PEX5结合,并在PEX5循环过程中被转运到过氧化物酶体腔中。这个货物转运步骤尚未完全了解,其能量学仍存在争议。我们使用随机计算模型来探索AAA ATP酶驱动的PEX5去除可能与哺乳动物细胞过氧化物酶体进口器中的货物转运耦合的不同方式。第一个考虑的模型是不耦合的,其中转运是自发的,并不立即依赖于PEX5的去除。第二个是直接耦合的,其中货物转运仅在其PEX5从过氧化物酶体膜上被去除时发生。第三个新模型是协同耦合的,需要给定进口体上的两个PEX5进行货物转运——一个带有相关货物的PEX5和一个带有泛素的PEX5。当我们改变基质蛋白货物向细胞质中的添加速率时,我们测量过氧化物酶体上的PEX5和泛素水平。我们发现,不耦合和直接耦合的转运在PEX5和泛素方面表现相同,并且随着基质蛋白流量的增加,过氧化物酶体泛素信号增加。相比之下,协同耦合的转运表现出显著不同,其泛素信号随着基质蛋白流量的增加而降低。最近的研究表明,哺乳动物过氧化物酶体膜上的泛素可导致自噬或“过氧化物酶体自噬”的选择性降解。因此,协同耦合蛋白转运中低基质货物流量时的高泛素水平可作为一种废弃信号来介导过氧化物酶体自噬。这种机制可能是细胞调节过氧化物酶体数量的一种方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c437/3894153/0b9d4b40f4bb/pcbi.1003426.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验