Cohen Yifat, Klug Yoel Alexander, Dimitrov Lazar, Erez Zohar, Chuartzman Silvia G, Elinger Dalia, Yofe Ido, Soliman Kareem, Gärtner Jutta, Thoms Sven, Schekman Randy, Elbaz-Alon Yael, Zalckvar Einat, Schuldiner Maya
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Mol Biosyst. 2014 Jul;10(7):1742-8. doi: 10.1039/c4mb00001c. Epub 2014 Apr 10.
Peroxisomes are ubiquitous and dynamic organelles that house many important pathways of cellular metabolism. In recent years it has been demonstrated that mitochondria are tightly connected with peroxisomes and are defective in several peroxisomal diseases. Indeed, these two organelles share metabolic routes as well as resident proteins and, at least in mammals, are connected via a vesicular transport pathway. However the exact extent of cross-talk between peroxisomes and mitochondria remains unclear. Here we used a combination of high throughput genetic manipulations of yeast libraries alongside high content screens to systematically unravel proteins that affect the transport of peroxisomal proteins and peroxisome biogenesis. Follow up work on the effector proteins that were identified revealed that peroxisomes are not randomly distributed in cells but are rather localized to specific mitochondrial subdomains such as mitochondria-ER junctions and sites of acetyl-CoA synthesis. Our approach highlights the intricate geography of the cell and suggests an additional layer of organization as a possible way to enable efficient metabolism. Our findings pave the way for further studying the machinery aligning mitochondria and peroxisomes, the role of the juxtaposition, as well as its regulation during various metabolic conditions. More broadly, the approaches used here can be easily applied to study any organelle of choice, facilitating the discovery of new aspects in cell biology.
过氧化物酶体是普遍存在且动态变化的细胞器，包含许多重要的细胞代谢途径。近年来，已有研究表明线粒体与过氧化物酶体紧密相连，且在几种过氧化物酶体疾病中存在缺陷。事实上，这两种细胞器共享代谢途径以及驻留蛋白，并且至少在哺乳动物中，它们通过囊泡运输途径相连。然而，过氧化物酶体与线粒体之间相互作用的确切程度仍不清楚。在这里，我们结合了对酵母文库的高通量基因操作和高内涵筛选，以系统地揭示影响过氧化物酶体蛋白运输和过氧化物酶体生物发生的蛋白质。对所鉴定的效应蛋白的后续研究表明，过氧化物酶体并非随机分布在细胞中，而是定位于特定的线粒体亚结构域，如线粒体 - 内质网连接点和乙酰辅酶A合成位点。我们的方法突出了细胞内错综复杂的结构，并提出了一种额外的组织层次，作为实现高效代谢的一种可能方式。我们的发现为进一步研究使线粒体和过氧化物酶体对齐的机制、并列的作用以及其在各种代谢条件下的调节铺平了道路。更广泛地说，这里使用的方法可以很容易地应用于研究任何选定的细胞器，有助于发现细胞生物学的新方面。
