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Journal of Biochemistry 2006 139(6):967-979; doi:10.1093/jb/mvj114
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© 2006 The Japanese Biochemical Society.

Regular Paper

Identification and Reverse Genetic Analysis of Mitochondrial Processing Peptidase and the Core Protein of the Cytochrome bc1 Complex of Caenorhabditis elegans, a Model Parasitic Nematode

Hiroyuki Nomura1, Senarath B. P. Athauda1,2, Hidenori Wada1, Yumiko Maruyama1, Kenji Takahashi1 and Hideshi Inoue1,*

1 Laboratory of Molecular Biochemistry, School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392; and 2 Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Peradeniya and Institute of Fundamental Studies, Kandy, Sri Lanka

* To whom correspondence should be addressed. Phone: +81 42 676 7256, Fax: +81 42 676 7256, E-mail: hinoue{at}ls.toyaku.ac.jp

Mitochondria could be a good target for anti-parasitic drugs. The {alpha} and ß subunits of mitochondrial processing peptidase (MPP) and the core subunits of the cytochrome bc1 complex, UCR-1 and UCR-2, are homologous to one another and are important for mitochondrial functions. However, our knowledge of these proteins in nematodes is very limited. Caenorhabditis elegans, a free-living nematode, has six genes coding for proteins homologous to these subunits. On primary structure comparison, and immunochemical and enzymological analyses, the gene products were assigned as follows: Y71G12B.24, {alpha}-MPP; ZC410.2, ß-MPP; F56D2.1, UCR-1; VW06B3R.1, T10B10.2; and T24C4.1, UCR-2. The primary structures of ß-MPP and UCR-1 from Brugia malayi, a parasitic nematode causing human filariasis, were deduced from their cDNA structures. Phylogenetic analysis showed that the UCR-1s from both C. elegans and B. malayi were less related to mammalian UCR-1s than to MPPs from various organisms. MPP and the bc1 complex are essential for the life cycle of C. elegans, because their reverse genetic inhibition is lethal. This suggests the possibility that these proteins are also essential for the viability of B. malayi and other parasitic nematodes, and are potential targets for anti-parasitic agents.


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