弗里德赖希共济失调中IRP1活性增加。

Increased IRP1 activity in Friedreich ataxia.

作者信息

Lobmayr Lioba, Brooks David G, Wilson Robert B

机构信息

University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Room 509A, Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, PA 19104, USA.

出版信息

Gene. 2005 Jul 18;354:157-61. doi: 10.1016/j.gene.2005.04.040.

DOI:10.1016/j.gene.2005.04.040

PMID:15970401

Abstract

In low-iron conditions, the cytosolic iron-regulatory protein IRP1 binds to iron-responsive elements (IREs) in mRNAs encoding iron-regulated proteins. In high-iron conditions, IRP1 incorporates an iron-sulfur cluster (ISC), which interferes with IRE binding and prevents intracellular iron accumulation. Here we demonstrate an incomplete shift of IRP1 to its ISC form in Friedreich ataxia (FRDA) fibroblasts, associated with decreased activities of ISC respiratory complexes. Our data suggest an impaired adaptive response to iron accumulation in FRDA cells.

摘要

在低铁条件下，胞质铁调节蛋白IRP1与编码铁调节蛋白的mRNA中的铁反应元件（IREs）结合。在高铁条件下，IRP1结合一个铁硫簇（ISC），这会干扰IRE结合并防止细胞内铁积累。在这里，我们证明在弗里德赖希共济失调（FRDA）成纤维细胞中，IRP1向其ISC形式的转变不完全，这与ISC呼吸复合体活性降低有关。我们的数据表明FRDA细胞对铁积累的适应性反应受损。