Department of Biological Sciences, University of North Texas, Denton TX 76203, USA.
The Alexander Silberman Institute of Life Science, Hebrew University of Jerusalem, Edmond J. Safra Campus at Givat Ram, Jerusalem 91904, Israel.
Sci Rep. 2017 Feb 16;7:42571. doi: 10.1038/srep42571.
NEET proteins belong to a unique family of iron-sulfur proteins in which the 2Fe-2S cluster is coordinated by a CDGSH domain that is followed by the "NEET" motif. They are involved in the regulation of iron and reactive oxygen metabolism, and have been associated with the progression of diabetes, cancer, aging and neurodegenerative diseases. Despite their important biological functions, the evolution and diversification of eukaryotic NEET proteins are largely unknown. Here we used the three members of the human NEET protein family (CISD1, mitoNEET; CISD2, NAF-1 or Miner 1; and CISD3, Miner2) as our guides to conduct a phylogenetic analysis of eukaryotic NEET proteins and their evolution. Our findings identified the slime mold Dictyostelium discoideum's CISD proteins as the closest to the ancient archetype of eukaryotic NEET proteins. We further identified CISD3 homologs in fungi that were previously reported not to contain any NEET proteins, and revealed that plants lack homolog(s) of CISD3. Furthermore, our study suggests that the mammalian NEET proteins, mitoNEET (CISD1) and NAF-1 (CISD2), emerged via gene duplication around the origin of vertebrates. Our findings provide new insights into the classification and expansion of the NEET protein family, as well as offer clues to the diverged functions of the human mitoNEET and NAF-1 proteins.
NEET 蛋白属于一类独特的铁硫蛋白家族，其中 2Fe-2S 簇由 CDGSH 结构域协调，其后是“NEET”基序。它们参与铁和活性氧代谢的调节，并与糖尿病、癌症、衰老和神经退行性疾病的进展有关。尽管它们具有重要的生物学功能，但真核 NEET 蛋白的进化和多样化在很大程度上是未知的。在这里，我们使用人类 NEET 蛋白家族的三个成员（CISD1、mitoNEET；CISD2、NAF-1 或 Miner 1；和 CISD3、Miner2）作为指南，对真核 NEET 蛋白及其进化进行了系统发育分析。我们的研究结果确定了粘菌 Dictyostelium discoideum 的 CISD 蛋白与真核 NEET 蛋白的古老原型最为接近。我们还在先前报道不含任何 NEET 蛋白的真菌中鉴定出 CISD3 同源物，并揭示植物缺乏 CISD3 的同源物。此外，我们的研究表明，哺乳动物的 NEET 蛋白 mitoNEET（CISD1）和 NAF-1（CISD2）是在脊椎动物起源时通过基因复制而出现的。我们的研究结果为 NEET 蛋白家族的分类和扩展提供了新的见解，并为人类 mitoNEET 和 NAF-1 蛋白的分化功能提供了线索。
