Biophysical characterization of the iron in mitochondria from Atm1p-depleted Saccharomyces cerevisiae.
Biophysical characterization of the iron in mitochondria from Atm1p-depleted Saccharomyces cerevisiae.
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DOI：
10.1021/bi901110n
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发表时间：
2009-10-13
期刊：
影响因子：
2.9
通讯作者：
Lindahl PA
中科院分区：
文献类型：
--
作者：
Miao R;Kim H;Koppolu UM;Ellis EA;Scott RA;Lindahl PA
Atm 1 p是一种定位于线粒体内膜的ABC转运蛋白，其功能是将未知物质输出到细胞质中，并参与细胞铁代谢。Atm 1 p的缺失或缺失导致线粒体中Fe的积累和胞质Fe/S簇组装的缺陷，但据报道线粒体Fe/S簇组装没有缺陷。在这项研究中，使用穆斯堡尔谱，EPR，电子吸收光谱，X射线吸收光谱和电子显微镜检查积累的铁的性质。在需氧生长的细胞中积累的Fe以Fe（III）磷酸盐纳米颗粒的形式存在，类似于在酵母共济失调蛋白Yfh 1 p缺失或酵母铁氧还蛋白Yah 1 p缺失的细胞中积累的Fe。相对于WT线粒体，Fe/S簇和血红素水平在Atm 1 p耗尽线粒体从有氧细胞显着减少。Atm 1 p-耗尽也造成了非血红素铁（II）离子在线粒体和氧化损伤的增加。从厌氧生长的细胞中分离的Atm 1 p耗尽的线粒体表现出WT水平的Fe/S簇和血红素，并且它们没有过度积累Fe。Atm 1 p耗尽的细胞缺乏Leu 1 p活性，无论它们是在有氧或厌氧条件下生长。这些结果表明，Atm 1 p不参与线粒体Fe/S簇组装，并且Atm 1 p输出的物种是胞质Fe/S簇组装所需的。Fe/S簇缺陷和Fe积累表型，导致在需氧细胞（但不是在厌氧细胞）的Atm 1 p的耗尽，可能是次要的影响，只有当细胞暴露于氧气生长过程中观察到。在这些条件下产生的活性氧可能会降解铁硫簇和降低血红素水平的细胞器。
Atm1p is an ABC transporter localized in the mitochondrial inner membrane; it functions to export an unknown species into the cytosol and is involved in cellular iron metabolism. Depletion or deletion of Atm1p causes Fe accumulation in mitochondria and a defect in cytosolic Fe/S cluster assembly, but reportedly not a defect in mitochondrial Fe/S cluster assembly. In this study the nature of the accumulated Fe was examined using Mössbauer spectroscopy, EPR, electronic absorption spectroscopy, X-ray absorption spectroscopy, and electron microscopy. The Fe that accumulated in aerobically grown cells was in the form of Fe(III) phosphate nanoparticles similar to that which accumulates in yeast frataxin Yfh1p-deleted or yeast ferredoxin Yah1p-depleted cells. Relative to WT mitochondria, Fe/S cluster and heme levels in Atm1p-depleted mitochondria from aerobic cells were significantly diminished. Atm1p-depletion also caused a build-up of nonheme Fe(II) ions in the mitochondria and an increase in oxidative damage. Atm1p-depleted mitochondria isolated from anaerobically grown cells exhibited WT levels of Fe/S clusters and hemes, and they did not hyper-accumulate Fe. Atm1p-depleted cells lacked Leu1p activity, regardless of whether they were grown aerobically or anaerobically. These results indicate that Atm1p does not participate in mitochondrial Fe/S cluster assembly, and that the species exported by Atm1p is required for cytosolic Fe/S cluster assembly. The Fe/S cluster defect and the Fe-accumulation phenotype, resulting from the depletion of Atm1p in aerobic cells (but not in anaerobic cells), may be secondary effects that are observed only when cells are exposed to oxygen during growth. Reactive oxygen species generated under these conditions might degrade iron-sulfur clusters and lower heme levels in the organelle.
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