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

Chen, Jian and Shi, Xiaoying and Padmanabhan, Ranjani and Wang, Qiong and Wu, Zhidan and Stevenson, Susan and Hild, Marc and Garza, Dan and Li, Hao (2008) Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster. Genome Research, 18 (1). pp. 123-136. ISSN 1088-9051

Abstract

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 on mitochondrial CS activity in transgenic flies or fly mutants. We confirmed a number of gene hits including HDAC6, Rpd3(HDAC1), CG3249, vimar, Src42A, klumpfuss, barren, and smt3 which exert effects on mitochondrial CS activities in vivo, demonstrating the value of Drosophila genome-wide RNAi screens for identifying genes and pathways that modulate mitochondrial function.

Item Type: Article
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Additional Information: free final full text version available at publisher's official URL and at PubMedCentral; archiving not formally supported by this publisher
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Date Deposited: 14 Dec 2009 14:01
Last Modified: 31 Jan 2013 01:19
URI: https://oak.novartis.com/id/eprint/342

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