BERG LLC, Framingham, MA, 01701, USA.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, 02-106, Poland.
Sci Rep. 2018 Apr 12;8(1):5915. doi: 10.1038/s41598-018-24305-2.
Heterologous expression is a landmark technique for studying a protein itself or its effect on the expression host, in which membrane-embedded proteins are a common choice. Yet, the impact of inserting a foreign protein to the lipid environment of host membranes, has never been addressed. Here we demonstrated that heterologous expression of the Artemia franciscana adenine nucleotide translocase (ANT) in yeasts altered lipidomic composition of their inner mitochondrial membranes. Along with this, activities of complex II, IV and ATP synthase, all membrane-embedded components, were significantly decreased while their expression levels remained unaffected. Although the results represent an individual case of expressing a crustacean protein in yeast inner mitochondrial membranes, it cannot be excluded that host lipidome alterations is a more widespread epiphenomenon, potentially biasing heterologous expression experiments. Finally, our results raise the possibility that not only lipids modulate protein function, but also membrane-embedded proteins modulate lipid composition, thus revealing a reciprocal mode of regulation for these two biomolecular entities.
异源表达是研究蛋白质本身或其对表达宿主影响的一项标志性技术，其中膜嵌入蛋白是常见的选择。然而，插入外源蛋白对宿主膜脂质环境的影响从未被涉及。在这里，我们证明了在酵母中异源表达卤虫腺嘌呤核苷酸转位酶（ANT）改变了其线粒体膜的脂质组学组成。与此相关的是，所有膜嵌入成分的复合物 II、IV 和 ATP 合酶的活性显著降低，而它们的表达水平保持不变。尽管这些结果代表了在酵母线粒体膜中表达甲壳动物蛋白的个别情况，但不能排除宿主脂质组改变是更普遍的表型现象，可能会使异源表达实验产生偏差。最后，我们的结果表明，不仅脂质调节蛋白质功能，而且膜嵌入蛋白质也调节脂质组成，从而揭示了这两种生物分子实体之间的一种相互调节模式。
