Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation.
Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation.
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DOI：
10.3389/fphar.2014.00130
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发表时间：
2014
影响因子：
5.6
通讯作者：
Puccio H
中科院分区：
文献类型：
--
作者：
Martelli A;Puccio H
弗里德赖希共济失调（FRDA）是高加索人群中最常见的隐性共济失调，其特征是脊髓小脑和感觉共济失调的混合，常与心肌病相关。这种疾病是由编码线粒体蛋白共济失调蛋白的FXN基因表达减少引起的。对患者样本的病理生理学的早期组织学和生物化学研究表明，铁代谢失调是该疾病的关键特征，主要特征在于线粒体铁积累和铁硫簇酶活性降低。近年来，通过细胞和生物化学方法，在理解frataxin的功能方面取得了相当大的进展，指出frataxin在铁硫簇生物发生中的主要作用。然而，为什么以及如何frataxin缺乏对这一重要的生物合成途径的影响导致线粒体铁积累仍然知之甚少。在此，我们回顾数据的主要功能和FRDA的铁代谢失调的性质的共济失调。到目前为止，线粒体铁超载在FRDA的病理生理意义仍有待澄清。
Friedreich ataxia (FRDA) is the most common recessive ataxia in the Caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia frequently associating cardiomyopathy. The disease results from decreased expression of the FXN gene coding for the mitochondrial protein frataxin. Early histological and biochemical study of the pathophysiology in patient's samples revealed that dysregulation of iron metabolism is a key feature of the disease, mainly characterized by mitochondrial iron accumulation and by decreased activity of iron-sulfur cluster enzymes. In the recent past years, considerable progress in understanding the function of frataxin has been provided through cellular and biochemical approaches, pointing to the primary role of frataxin in iron-sulfur cluster biogenesis. However, why and how the impact of frataxin deficiency on this essential biosynthetic pathway leads to mitochondrial iron accumulation is still poorly understood. Herein, we review data on both the primary function of frataxin and the nature of the iron metabolism dysregulation in FRDA. To date, the pathophysiological implication of the mitochondrial iron overload in FRDA remains to be clarified.
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影响因子：
29
作者：
Anderson SA;Nizzi CP;Chang YI;Deck KM;Schmidt PJ;Galy B;Damnernsawad A;Broman AT;Kendziorski C;Hentze MW;Fleming MD;Zhang J;Eisenstein RS
通讯作者：
Eisenstein RS
影响因子：
3.5
作者：
Anderson, PR;Kirby, K;Phillips, JP
通讯作者：
Phillips, JP
DOI：
10.1073/pnas.94.14.7452
发表时间：
1997-07-08
影响因子：
11.1
作者：
Cossee, M;Schmitt, M;Koenig, M
通讯作者：
Koenig, M
影响因子：
5.3
作者：
Biederbick, Annette;Stehling, Oliver;Lill, Roland
通讯作者：
Lill, Roland
影响因子：
4.4
作者：
Bradley, JL;Homayoun, S;Cooper, JM
通讯作者：
Cooper, JM