Genome-Wide Localization Study of Yeast Pex11 Identifies Peroxisome-Mitochondria Interactions through the ERMES Complex.
Genome-Wide Localization Study of Yeast Pex11 Identifies Peroxisome-Mitochondria Interactions through the ERMES Complex.
复制标题
酵母PEX11的全基因组定位研究通过ERMES复合物鉴定过过氧化物酶体的相互作用。
DOI：
10.1016/j.jmb.2015.03.004
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发表时间：
2015-06-05
影响因子：
5.6
通讯作者：
Petrovic, U.
中科院分区：
文献类型：
--
作者：
Usaj, M. Mattiazzi;Brloznik, M.;Kaferle, P.;Zitnik, M.;Wolinski, H.;Leitner, F.;Kohlwein, S. D.;Zupan, B.;Petrovic, U.
关键词：
Pex 11是一种过氧化物酶，调节真核细胞中过氧化物酶体的数量。最近，人们发现三种哺乳动物旁系同源基因之一的突变PEX 11 β会导致神经系统疾病。然而，Pex 11的分子功能尚不清楚。酿酒酵母Pex 11已被证明招募过氧化物酶体的线粒体裂变机制，从而使过氧化物酶体的增殖。该过程对于有效的脂肪酸β-氧化至关重要。在这项研究中，我们使用全基因组规模的高含量显微镜来确定酵母Pex 11在所有非必需基因缺失突变体以及温度敏感性必需基因突变体中的亚细胞定位模式。过氧化物酶体的Pex 11定位和形态受到功能分类的104个不同基因突变的深刻影响。更详细地分析了编码ERMES复合物的线粒体和胞质组分的一组基因，包括MDM 10、MDM 12和MDM 34。这些基因的缺失引起了一个专门改变Pex 11定位模式，而删除MMM 1，基因编码的第四，内质网相关的复杂的组成部分，并没有导致改变Pex 11定位或过氧化物酶体形态表型。此外，我们发现Pex 11和Mdm 34物理相互作用，Pex 11通过ERMES复合物在建立过氧化物酶体和线粒体之间的接触位点中发挥作用。基于这些结果，我们提出ERMES复合物的线粒体/胞质组分通过Pex 11建立线粒体和过氧化物酶体之间的直接相互作用。Pex 11是一种在代谢和疾病中起作用的蛋白质，其分子功能尚不清楚。全基因组筛选确定了Pex 11-GFP在酵母中的亚细胞定位。ERMES复合物组分缺陷的突变体显示改变的Pex 11定位。Pex 11与ERMES复合物组分Mdm 34物理相互作用。ERMES复合物和Pex 11介导线粒体和过氧化物酶体之间的相互作用。
Pex11 is a peroxin that regulates the number of peroxisomes in eukaryotic cells. Recently, it was found that a mutation in one of the three mammalian paralogs, PEX11β, results in a neurological disorder. The molecular function of Pex11, however, is not known. Saccharomyces cerevisiae Pex11 has been shown to recruit to peroxisomes the mitochondrial fission machinery, thus enabling proliferation of peroxisomes. This process is essential for efficient fatty acid β-oxidation. In this study, we used high-content microscopy on a genome-wide scale to determine the subcellular localization pattern of yeast Pex11 in all non-essential gene deletion mutants, as well as in temperature-sensitive essential gene mutants. Pex11 localization and morphology of peroxisomes was profoundly affected by mutations in 104 different genes that were functionally classified. A group of genes encompassing MDM10, MDM12 and MDM34 that encode the mitochondrial and cytosolic components of the ERMES complex was analyzed in greater detail. Deletion of these genes caused a specifically altered Pex11 localization pattern, whereas deletion of MMM1, the gene encoding the fourth, endoplasmic-reticulum-associated component of the complex, did not result in an altered Pex11 localization or peroxisome morphology phenotype. Moreover, we found that Pex11 and Mdm34 physically interact and that Pex11 plays a role in establishing the contact sites between peroxisomes and mitochondria through the ERMES complex. Based on these results, we propose that the mitochondrial/cytosolic components of the ERMES complex establish a direct interaction between mitochondria and peroxisomes through Pex11. Molecular function of Pex11, a protein with roles in metabolism and disease, is unknown. Genome-wide screening determined subcellular localization of Pex11-GFP in yeast. Mutants defective in components of the ERMES complex show altered Pex11 localization. Pex11 physically interacts with the ERMES complex component Mdm34. ERMES complex and Pex11 mediate interaction between mitochondria and peroxisomes.
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