Alkhateeb Ahmed A, Connor James R
Department of Neurosurgery, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Biochim Biophys Acta. 2010 Aug;1800(8):793-7. doi: 10.1016/j.bbagen.2010.03.017. Epub 2010 Mar 25.
Ferritin has been traditionally considered a cytoplasmic iron storage protein. However, several studies over the last two decades have reported the nuclear localization of ferritin, specifically H-ferritin, in developing neurons, hepatocytes, corneal epithelial cells, and some cancer cells. These observations encouraged a new perspective on ferritin beyond iron storage, such as a role in the regulation of iron accessibility to nuclear components, DNA protection from iron-induced oxidative damage, and transcriptional regulation.
This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease.
The nuclear translocation of ferritin is a selective energy-dependent process that does not seem to require a consensus nuclear localization signal. It is still unclear what regulates the nuclear import/export of ferritin. Some reports have implicated the phosphorylation and O-glycosylation of the ferritin protein in nuclear transport; others suggested the existence of a specific nuclear chaperone for ferritin. The data argue strongly for nuclear ferritin as a factor in human development and disease. Ferritin can bind and protect DNA from oxidative damage. It also has the potential of playing a regulatory role in transcription.
Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule.
铁蛋白传统上被认为是一种细胞质铁储存蛋白。然而，在过去二十年中的多项研究报告了铁蛋白，特别是H-铁蛋白，在发育中的神经元、肝细胞、角膜上皮细胞和一些癌细胞中的核定位。这些观察结果促使人们对铁蛋白有了超越铁储存的新认识，比如在调节铁进入核成分的可及性、保护DNA免受铁诱导的氧化损伤以及转录调控方面的作用。
本综述将探讨在人类发育和疾病背景下核铁蛋白的转运及其功能意义。
铁蛋白的核转运是一个选择性的能量依赖过程，似乎不需要一致的核定位信号。目前仍不清楚是什么调节铁蛋白的核输入/输出。一些报告表明铁蛋白蛋白的磷酸化和O-糖基化与核转运有关；另一些则提出存在一种针对铁蛋白的特定核伴侣蛋白。有充分的数据表明核铁蛋白是人类发育和疾病中的一个因素。铁蛋白可以结合并保护DNA免受氧化损伤。它还具有在转录中发挥调节作用的潜力。
核铁蛋白代表了铁蛋白功能的一种新观点，超越了其作为铁储存分子的经典作用。
