線粒體是細胞中將食物轉化為能量的一種微型結構，它存在于每一個細胞。 據最新的《自然─生物技術》（Nature Biotechnology）報道，一項針對 2500多種藥物和自然物品對線粒體影響的分析項目已經啟動，有望給從事糖 尿病、神經退化性疾病甚至老年症研究的科學家提供無價之寶，也有助于闡 明線粒體在健康和疾病中的作用。 在小鼠肌肉中的線粒體中，Vamsi Mootha和同事監測了線粒體對各種藥物的 生理學反應和基因表達。這些數據將用于尋找新線索，預示已批準藥物的新 作用和副作用。比如，現有的分析支持這樣的觀點，即有缺陷的線粒體可能 與服用“他汀”所導致的肌肉痙攣有關，“他汀”是一種降血脂藥物，世界 有1億人在服用這種藥物。 另外一個意外收獲是，他們發現了線粒體的基因表達與微管陣列之間的一種 聯系。微管陣列是一種“腳手架”，它像高速公路一樣在細胞間運送關鍵分 子。在治療糖尿病的某種傳統中藥中，其治療作用可能源于某種成分擁有打 破微管陣列的能力。 Large-scale chemical dissection of mitochondrial function Bridget K Wagner1,5, Toshimori Kitami1,2,5, Tamara J Gilbert1, David Peck1, Arvind Ramanathan1, Stuart L Schreiber1, Todd R Golub1,3 & Vamsi K Mootha1,2,4 Abstract Mitochondrial oxidative phosphorylation (OXPHOS) is under the control of both mitochondrial (mtDNA) and nuclear genomes and is central to energy homeostasis. To investigate how its function and regulation are integrated within cells, we systematically combined four cell-based assays of OXPHOS physiology with multiplexed measurements of nuclear and mtDNA gene expression across 2,490 small-molecule perturbations in cultured muscle. Mining the resulting compendium revealed, first, that protein synthesis inhibitors can decouple coordination of nuclear and mtDNA transcription; second, that a subset of HMG-CoA reductase inhibitors, combined with propranolol, can cause mitochondrial toxicity, yielding potential clues about the etiology of statin myopathy; and, third, that structurally diverse microtubule inhibitors stimulate OXPHOS transcription while suppressing reactive oxygen species, via a transcriptional mechanism involving PGC-1 and ERR, and thus may be useful in treating age-associated degenerative disorders. Our screening compendium can be used as a discovery tool both for understanding mitochondrial biology and toxicity and for identifying novel therapeutics. --

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