线粒体铁代谢与人类疾病的研究进展

线粒体铁代谢的研究主要包括两个方面：铁在胞质和线粒体之间的转运和调控；铁硫簇和血红素在线粒体内的合成与转运。目前认为线粒体铁的转入主要是与mitoferrinl／2（MFRNl和MFRN2）和ABCBl0有关，运出可能与ABCB6和／或ABCB7有关，转运和调控的具体机制不是很清楚，推测与某种含有铁硫簇的信号分子有关。哺乳动物铁硫簇的合成可以发生在胞质和线粒体内，但以线粒体为主；真核生物中与铁硫簇合成相关的蛋白达二十多种，其中FXN、ISCS、ISDll和ISCU及其同系物被认为是核心组分。血红素的合成起始和终止发生在线粒体内，终止步骤为亚铁螯合酶将铁插入原卟啉IX，该酶活性又依赖于铁硫簇。因此，铁硫簇的合成与调控是线粒体铁代谢的核心，也是整个细胞铁运作的核心。本文主要围绕线粒体铁代谢特别是铁硫簇的合成异常引起的疾病做一简单的综述。

Recent progress on mitochondrial iron metabolism and human diseases

Two aspects of mitochondrial iron metabolism are included： iron trafficking and communication between cytosol and mitochondria; iron-sulfur clusters （Fe-S） and heme biogenesis in mitochondria and transport from mitochondria into extramitochondria. Recent investigations have identified a host of mitochondrial proteins that may play roles in the homeostasis of mitochondrial iron. For instance, mitoferrins 1 and 2 （MFRN1 and MFRN2） and ABCB 10 are thought to be involved in iron trafficking from cytosol to mitochondria, while ABCB 6 and/or 7 are in reverse direction of iron trafficking. The detailed trafficking and regulation remain unknown, whereas it is suspected that a Fe-S protein as an iron sensor is involved in communication between mitochondria and extramitochondria. Mammalian Fe-S biogenesis is thought to occur mainly in mitochondria, as well as in cytosol. Totally more than 20proteins are currently found to be involved in Fe-S cluster biogenesis in eukaryotes, four of which, ISCS, ISDll, ISCU, and FXN, are considered to be core.components of the machinery. Initiation and termination of heine biogen- esis take place in mitochondria. And the last step is iron insertion into protoporphrin IX by ferrochelatase to form heme. Mammalian ferrochelatase activity is 2Fe-2S-dependent. Thus, F＇e-S biogenesis and regulation play a vital role in mitochondrial iron metabolism and in whole-cell iron processing. This paper will summarize the recent progress on mitochondrial iron metabolism, particularly Fe-S cluster biogenesis and human diseases caused by impairment of Fe-S cluster assembly or trafficking.