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Journal of Biochemistry Advance Access originally published online on January 2, 2008
Journal of Biochemistry 2008 143(4):449-454; doi:10.1093/jb/mvm245
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© 2008 The Japanese Biochemical Society.

An RNAi Screen for Mitochondrial Proteins Required to Maintain the Morphology of the Organelle in Caenorhabditis elegans

Ryohei Ichishita, Kousuke Tanaka, Yoshimi Sugiura, Tomoko Sayano, Katsuyoshi Mihara and Toshihiko Oka*

Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan

*To whom correspondence should be addressed. Tel: +81-92-642-6178, Fax: +81-92-642-6183, E-mail: okat{at}cell.med.kyushu-u.ac.jp

Received December 7, 2007; Accepted December 7, 2007


   Abstract

Mitochondria are dynamic organelles that frequently divide and fuse together, resulting in the formation of intracellular tubular networks. In yeast and mammals, several factors including Drp1/Dnm1 and Mfn/Fzo1 are known to regulate mitochondrial morphology by controlling membrane fission or fusion. Here, we report the systematic screening of Caenorhabditis elegans mitochondrial proteins required to maintain the morphology of the organelle using an RNA interference feeding library. In C. elegans body wall muscle cells, mitochondria usually formed tubular structures and were severely fragmented by the mutation in fzo-1 gene, indicating that the body wall muscle cells are suitable for monitoring changes in mitochondrial morphology due to gene silencing. Of 719 genes predicted to code for most of mitochondrial proteins, knockdown of >80% of them caused abnormal mitochondrial morphology, including fragmentation and elongation. These findings indicate that most fundamental mitochondrial functions, including metabolism and oxidative phosphorylation, are necessary for maintenance of the tubular networks as well as membrane fission and fusion. This is the first evidence that known mitochondrial activities are prerequisite for regulating the morphology of the organelle. Furthermore, 88 uncharacterized or poorly characterized genes were found in the screening to be implicated in mitochondrial morphology.

Key Words: Caenorhabditis elegans, elongation, fragmentation, mitochondrial morphology, RNAi screening

Abbreviations: AAT, aspartate aminotransferase; GFP, green fluorescent protein; MitoP2, Mitochondria Proteome database; mRFP, monomeric red fluorescent protein; RNAi, RNA interference


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