Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes.
Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes.
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DOI：
10.3389/fphar.2014.00061
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发表时间：
2014
影响因子：
5.6
通讯作者：
Tolosano E
中科院分区：
文献类型：
--
作者：
Chiabrando D;Vinchi F;Fiorito V;Mercurio S;Tolosano E
血红素(铁原卟啉IX)是一种重要的辅因子，参与多种生物过程：氧的运输和储存、电子传递、药物和类固醇代谢、信号转导和微小RNA加工。然而，过量的游离血红素具有很强的毒性，因为它能够促进氧化应激和脂质过氧化，从而导致膜损伤，最终导致细胞凋亡。因此，需要对血红素新陈代谢进行精细调控。细胞内的血红素数量受到多个水平的控制：合成、被血红素蛋白利用、降解以及细胞内和细胞间的运输。这篇综述主要集中在最近的发现，强调了控制细胞内的血红素水平以对抗血红素诱导的氧化应激的重要性。讨论了从细胞外环境中清除血红素、血红素合成和并入血红素蛋白、血红素分解代谢和血红素运输在维持足够的细胞内血红素含量方面的贡献。特别关注最近描述的由特定的血红素进口商和出口商介导的通过质膜的血红素运输机制。最后，说明了控制血红素代谢的基因在几种病理条件下的参与，并讨论了旨在控制血红素代谢的新的治疗方法。
Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is highly toxic due to its ability to promote oxidative stress and lipid peroxidation, thus leading to membrane injury and, ultimately, apoptosis. Thus, heme metabolism needs to be finely regulated. Intracellular heme amount is controlled at multiple levels: synthesis, utilization by hemoproteins, degradation and both intracellular and intercellular trafficking. This review focuses on recent findings highlighting the importance of controlling intracellular heme levels to counteract heme-induced oxidative stress. The contributions of heme scavenging from the extracellular environment, heme synthesis and incorporation into hemoproteins, heme catabolism and heme transport in maintaining adequate intracellular heme content are discussed. Particular attention is put on the recently described mechanisms of heme trafficking through the plasma membrane mediated by specific heme importers and exporters. Finally, the involvement of genes orchestrating heme metabolism in several pathological conditions is illustrated and new therapeutic approaches aimed at controlling heme metabolism are discussed.
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