Iron Metabolism and Chelation Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia.
Antioxid Redox Signal. 2011 Dec 15;15(12):3003-19. doi: 10.1089/ars.2011.3921. Epub 2011 May 5.
The mitochondrion plays vital roles in various aspects of cellular metabolism, ranging from energy transduction and apoptosis to the synthesis of important molecules such as heme. Mitochondria are also centrally involved in iron metabolism, as exemplified by disruptions in mitochondrial proteins that lead to perturbations in whole-cell iron processing. Recent investigations have identified a host of mitochondrial proteins (e.g., mitochondrial ferritin; mitoferrins 1 and 2; ABCBs 6, 7, and 10; and frataxin) that may play roles in the homeostasis of mitochondrial iron. These mitochondrial proteins appear to participate in one or more processes of iron storage, iron uptake, and heme and iron-sulfur cluster synthesis. In this review, we present and critically discuss the evidence suggesting that the mitochondrion may contribute to the regulation of whole-cell iron metabolism. Further, human diseases that arise from a dysregulation of these mitochondrial molecules reveal the ability of the mitochondrion to communicate with cytosolic iron metabolism to coordinate whole-cell iron processing and to fulfill the high demands of this organelle for iron. This review highlights new advances in understanding iron metabolism in terms of novel molecular players and diseases associated with its dysregulation.
线粒体在细胞代谢的各个方面发挥着重要作用，从能量转导和细胞凋亡到血红素等重要分子的合成。线粒体还在铁代谢中起着核心作用，例如线粒体蛋白的破坏会导致整个细胞铁处理的紊乱。最近的研究已经确定了许多线粒体蛋白（例如线粒体铁蛋白；mitoferrins1 和 2；ABCBs6、7 和 10；和 frataxin）可能在维持线粒体铁的稳态中发挥作用。这些线粒体蛋白似乎参与了铁储存、铁摄取、血红素和铁硫簇合成的一个或多个过程。在这篇综述中，我们提出并批判性地讨论了表明线粒体可能有助于调节整个细胞铁代谢的证据。此外，由于这些线粒体分子的失调而引起的人类疾病表明，线粒体能够与细胞质铁代谢进行通讯，以协调整个细胞的铁处理，并满足该细胞器对铁的高需求。这篇综述强调了理解铁代谢方面的新进展，涉及新的分子参与者和与其失调相关的疾病。
