2012年11月23日 讯 /生物谷BIOON/ --近日，科学家发现一种新形式铁的存在有助开发出一种致命遗传性神经系统疾病弗立特里希氏共济失调有效治疗方式，这类疾病会导致步态不稳、言语障碍、心脏疾病、糖尿病等症状。
在今天的PNAS杂志上刊出的一项研究中，研究人员在一种罕见疾病弗立特里希氏共济失调的研究中或的论文突破性进展。论文合著者教授Tim St Pierre和Lucia Gutierrez分析了铁在患者身体中的作用，并采用了新方法衡量和检测了患者体内的铁。
博士研究生Adam Fleming等人发现一个尚未被命名的新形式的铁存在于患有该疾病的小鼠心脏中。研究人员利用包括穆斯堡尔能谱学和磁化率等新技术测量了小鼠心脏中的铁，并试图找出含铁的物质，这些物质最初只在电子显微镜下初步观察到。
实验在5开尔文或零下268摄氏度的低温下进行。St Pierre教授说：在弗立特里希氏共济失调患者中，细胞中的铁结合蛋白是不存在或表达减少的。也即患者体内铁代谢发生了改变，细胞线粒体比正常水平含有更多的铁，而细胞质的铁比正常情况少。过量的铁可能会导致出现问题，而缺铁也会导致问题。特别是器官的铁过量容易导致有害自由基的积累。（生物谷：Bioon.com）
doi:10.1073/pnas.1215349109
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Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia
Megan Whitnalla, Yohan Suryo Rahmantoa, Michael L.-H. Huanga, et al.
There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich ataxia (FA). This disease is due to decreased expression of the mitochondrial protein, frataxin, which leads to alterations in mitochondrial iron (Fe) metabolism. The identification of potentially toxic mitochondrial Fe deposits in FA suggests Fe plays a role in its pathogenesis. Studies using the muscle creatine kinase (MCK) conditional frataxin knockout mouse that mirrors the disease have demonstrated frataxin deletion alters cardiac Fe metabolism. Indeed, there are pronounced changes in Fe trafficking away from the cytosol to the mitochondrion, leading to a cytosolic Fe deficiency. Considering Fe deficiency can induce apoptosis and cell death, we examined the effect of dietary Fe supplementation, which led to body Fe loading and limited the cardiac hypertrophy in MCK mutants. Furthermore, this study indicates a unique effect of heart and skeletal muscle-specific frataxin deletion on systemic Fe metabolism. Namely, frataxin deletion induces a signaling mechanism to increase systemic Fe levels and Fe loading in tissues where frataxin expression is intact (i.e., liver, kidney, and spleen). Examining the mutant heart, native size-exclusion chromatography, transmission electron microscopy, M?ssbauer spectroscopy, and magnetic susceptibility measurements demonstrated that in the absence of frataxin, mitochondria contained biomineral Fe aggregates, which were distinctly different from isolated mammalian ferritin molecules. These mitochondrial aggregates of Fe, phosphorus, and sulfur, probably contribute to the oxidative stress and pathology observed in the absence of frataxin.
