Napier Ian, Ponka Prem, Richardson Des R
Children's Cancer Institute Australia for Medical Research, Iron Metabolism and Chelation Program, PO Box 81, High St, Randwick, Sydney, New South Wales, 2031 Australia.
Blood. 2005 Mar 1;105(5):1867-74. doi: 10.1182/blood-2004-10-3856. Epub 2004 Nov 4.
It is well known that iron (Fe) is transported to the mitochondrion for heme synthesis. However, only recently has the importance of this organelle for many other facets of Fe metabolism become widely appreciated. Indeed, this was stimulated by the description of human disease states that implicate mitochondrial Fe metabolism. In particular, studies assessing various diseases leading to mitochondrial Fe loading have produced intriguing findings. For instance, the disease X-linked sideroblastic anemia with ataxia (XLSA/A) is due to a mutation in the ATP-binding cassette protein B7 (ABCB7) transporter that is thought to transfer [Fe-S] clusters from the mitochondrion to the cytoplasm. This and numerous other findings suggest the mitochondrion is a dynamo of Fe metabolism, being vital not only for heme synthesis but also for playing a critical role in the genesis of [Fe-S] clusters. Studies examining the disease Friedreich ataxia have suggested that a mutation in the gene encoding frataxin leads to mitochondrial Fe loading. Apart from these findings, the recently discovered mitochondrial ferritin that may store Fe in ring sideroblasts could also regulate the level of Fe needed for heme and [Fe-S] cluster synthesis. In this review, we suggest a model of mitochondrial Fe processing that may account for the pathology observed in these disease states.
众所周知，铁（Fe）被转运到线粒体用于血红素合成。然而，直到最近，这种细胞器在铁代谢的许多其他方面的重要性才得到广泛认可。事实上，这是由涉及线粒体铁代谢的人类疾病状态的描述所激发的。特别是，评估各种导致线粒体铁过载的疾病的研究产生了有趣的发现。例如，X连锁铁粒幼细胞贫血伴共济失调（XLSA/A）疾病是由于ATP结合盒蛋白B7（ABCB7）转运体的突变引起的，该转运体被认为将[Fe-S]簇从线粒体转移到细胞质中。这一发现以及许多其他发现表明，线粒体是铁代谢的动力源，不仅对血红素合成至关重要，而且在[Fe-S]簇的形成中也起着关键作用。对弗里德赖希共济失调疾病的研究表明，编码frataxin的基因突变会导致线粒体铁过载。除了这些发现外，最近发现的线粒体铁蛋白可能在环形铁粒幼细胞中储存铁，也可能调节血红素和[Fe-S]簇合成所需的铁水平。在这篇综述中，我们提出了一个线粒体铁加工模型，该模型可能解释在这些疾病状态中观察到的病理情况。
