Nature Biotechnology：药物对线粒体的影响分析

线粒体是细胞中将食物转化为能量的一种微型结构，它存在于每一个细胞。据最新的《自然—生物技术》（Nature Biotechnology）报道，一项针对2500多种药物和自然物品对线粒体影响的分析项目已经启动，有望给从事糖尿病、神经退化性疾病甚至老年症研究的科学家提供无价之宝，也有助于阐明线粒体在健康和疾病中的作用。

在小鼠肌肉中的线粒体中，Vamsi Mootha和同事监测了线粒体对各种药物的生理学反应和基因表达。这些数据将用于寻找新线索，预示已批准药物的新作用和副作用。比如，现有的分析支持这样的观点，即有缺陷的线粒体可能与服用“他汀”所导致的肌肉痉挛有关，“他汀”是一种降血脂药物，世界有1亿人在服用这种药物。

另外一个意外收获是，他们发现了线粒体的基因表达与微管阵列之间的一种联系。微管阵列是一种“脚手架”，它像高速公路一样在细胞间运送关键分子。在治疗糖尿病的某种传统中药中，其治疗作用可能源于某种成分拥有打破微管阵列的能力。

原始出处：


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