Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster

被引：46

作者：

Chen, Jian ^{[1
]}

Shi, Xiaoying ^{[1
]}

Padmanabhan, Ranjani ^{[1
]}

Wang, Qiong ^{[1
]}

Wu, Zhidan ^{[2
]}

Stevenson, Susan C. ^{[2
]}

Hild, Marc ^{[1
]}

Garza, Dan ^{[1
]}

Li, Hao ^{[3
]}

机构：

[1] Novartis Inst Biomed Res, Cambridge, MA 02139 USA

[2] Novartis Inst Biomed Res, Diabet & Metabol Dis Area, Cambridge, MA 02139 USA

[3] Novartis Inst Biomed Res, NIBR Patents, Cambridge, MA 02139 USA

来源：

GENOME RESEARCH | 2008年 / 18卷 / 01期

关键词：

D O I：

10.1101/gr.6940108

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Mitochondrial dysfunction is associated with many human diseases. There has not been a systematic genetic approach for identifying regulators of basal mitochondrial biogenesis and function in higher eukaryotes. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells using mitochondrial Citrate synthase [CS) activity as the primary readout. We screened 13,071 dsRNAs and identified 152 genes that modulate CS activity. These modulators are involved in a wide range of biological processes and pathways including mitochondrial-related functions, transcriptional and translational regulation, and signaling pathways. Selected hits among the 152 genes were further analyzed for their effect oil rnitochondrial CS activity in transgenic flies or fly mutants. We confirmed a number of gene hits including HDAC6, Rpd3(HDACI), CG3249, vimar, Src42A, klumpfuss, barren, and smt3 which exert effects on mitochondrial CS activities ill vivo, demonstrating the value of Drosophila genome-wide RNAi screens for identifying genes and pathways that modulate mitochondrial function.

引用

页码：123 / 136

页数：14

共 87 条

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