Peroxisomes are juxtaposed to strategic sites on mitochondria
Peroxisomes are juxtaposed to strategic sites on mitochondria
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DOI：
10.1039/c4mb00001c
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Schuldiner, Maya
中科院分区：
文献类型：
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作者：
Cohen, Yifat;Klug, Yoel Alexander;Schuldiner, Maya
过氧化物酶体是一种普遍存在的动态细胞器，在细胞代谢中起着重要的作用。近年来研究表明，线粒体与过氧化物酶体紧密相连，并在多种过氧化物酶体疾病中存在缺陷。事实上，这两个细胞器共享代谢途径以及常驻蛋白质，并且至少在哺乳动物中，通过囊泡运输途径连接。然而，过氧化物酶体和线粒体之间的串扰的确切程度仍不清楚。在这里，我们使用了酵母文库的高通量遗传操作与高含量筛选的组合，以系统地解开影响过氧化物酶体蛋白和过氧化物酶体生物合成的转运的蛋白。对所鉴定的效应蛋白的后续工作显示，过氧化物酶体不是随机分布在细胞中，而是定位于特定的线粒体亚结构域，例如线粒体-ER连接和乙酰辅酶A合成位点。我们的方法突出了细胞复杂的地理结构，并建议增加一层组织作为实现有效代谢的可能途径。我们的研究结果为进一步研究线粒体和过氧化物酶体的排列机制、并列的作用以及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择的细胞器，促进细胞生物学新方面的发现。
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.