Mense Sarah M, Zhang Li
Department of Environmental Health Sciences, Columbia University, Mailman School of Public Health, New York, NY 10032, USA.
Cell Res. 2006 Aug;16(8):681-92. doi: 10.1038/sj.cr.7310086.
Heme (iron protoporphyrin IX) is an essential molecule for numerous living organisms. Not only does it serve as a prosthetic group in enzymes, it also acts as a signaling molecule that controls diverse molecular and cellular processes ranging from signal transduction to protein complex assembly. Deficient heme synthesis or function impacts the hematopoietic, hepatic and nervous systems in humans. Recent studies have revealed a series of heme-regulated transcription factors and signal transducers including Hap1, a heme-activated transcription factor that mediates the effects of oxygen on gene transcription in the yeast Saccharomyces cerevisiae; Bach1, a transcriptional repressor that is negatively regulated by heme in mammalian cells; IRR, an iron regulatory protein that mediates the iron-dependant regulation of heme synthesis in the bacterium Bradyrhizobium japonicum; and heme-regulated inhibitor, an eucaryotic initiation factor 2alpha kinase that coordinates protein synthesis with heme availability in reticulocytes. In this review, we summarize the current knowledge about how heme controls the activity of these transcriptional regulators and signal transducers, and discuss diseases associated with defective heme synthesis, degradation and function.
血红素（铁原卟啉IX）是许多生物体内的必需分子。它不仅作为酶的辅基，还作为一种信号分子，控制从信号转导到蛋白质复合物组装等多种分子和细胞过程。血红素合成或功能缺陷会影响人类的造血、肝脏和神经系统。最近的研究揭示了一系列血红素调节的转录因子和信号转导分子，包括Hap1，一种血红素激活的转录因子，介导氧气对酿酒酵母基因转录的影响；Bach1，一种转录抑制因子，在哺乳动物细胞中受血红素负调控；IRR，一种铁调节蛋白，介导日本慢生根瘤菌中血红素合成的铁依赖性调节；以及血红素调节抑制剂，一种真核起始因子2α激酶，在网织红细胞中协调蛋白质合成与血红素可用性。在这篇综述中，我们总结了目前关于血红素如何控制这些转录调节因子和信号转导分子活性的知识，并讨论了与血红素合成、降解和功能缺陷相关的疾病。
