RT Journal
A1 Chen, Jian
A1 Shi, Xiaoying
A1 Padmanabhan, Ranjani
A1 Wang, Qiong
A1 Wu, Zhidan
A1 Stevenson, Susan C.
A1 Hild, Marc
A1 Garza, Dan
A1 Li, Hao
T1 Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster
JF Genome Research 
JO Genome Research 
YR 2008 
FD January 01 
VO 18 
IS 1 
SP 123 
OP 136 
DO 10.1101/gr.6940108 
UL http://genome.cshlp.org/content/18/1/123.abstract 
AB 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.