Ahmed A Alkhateeb1, James R Connor. 1. Department of Neurosurgery, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Abstract
BACKGROUND: 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. SCOPE OF REVIEW: This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule. Copyright 2010 Elsevier B.V. All rights reserved.
BACKGROUND: 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. SCOPE OF REVIEW: This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule. Copyright 2010 Elsevier B.V. All rights reserved.