2012年11月23日 訊 /生物谷BIOON/ --近日,，科學(xué)家發(fā)現(xiàn)一種新形式鐵的存在有助開發(fā)出一種致命遺傳性神經(jīng)系統(tǒng)疾病弗立特里希氏共濟(jì)失調(diào)有效治療方式,，這類疾病會(huì)導(dǎo)致步態(tài)不穩(wěn)、言語障礙,、心臟疾病,、糖尿病等癥狀。
在今天的PNAS雜志上刊出的一項(xiàng)研究中,，研究人員在一種罕見疾病弗立特里希氏共濟(jì)失調(diào)的研究中或的論文突破性進(jìn)展,。論文合著者教授Tim St Pierre和Lucia Gutierrez分析了鐵在患者身體中的作用，并采用了新方法衡量和檢測(cè)了患者體內(nèi)的鐵,。
博士研究生Adam Fleming等人發(fā)現(xiàn)一個(gè)尚未被命名的新形式的鐵存在于患有該疾病的小鼠心臟中,。研究人員利用包括穆斯堡爾能譜學(xué)和磁化率等新技術(shù)測(cè)量了小鼠心臟中的鐵，并試圖找出含鐵的物質(zhì),，這些物質(zhì)最初只在電子顯微鏡下初步觀察到,。
實(shí)驗(yàn)在5開爾文或零下268攝氏度的低溫下進(jìn)行。St Pierre教授說：在弗立特里希氏共濟(jì)失調(diào)患者中,，細(xì)胞中的鐵結(jié)合蛋白是不存在或表達(dá)減少的,。也即患者體內(nèi)鐵代謝發(fā)生了改變，細(xì)胞線粒體比正常水平含有更多的鐵,，而細(xì)胞質(zhì)的鐵比正常情況少,。過量的鐵可能會(huì)導(dǎo)致出現(xiàn)問題，而缺鐵也會(huì)導(dǎo)致問題,。特別是器官的鐵過量容易導(dǎo)致有害自由基的積累,。（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.
