Mitochondria can be a good target for anti-parasitic drugs. The vast majorities of mitochondrial proteins are synthesized in cytoplasm as precursors with an N-terminal extension peptide for targeting to mitochondria. Mitochondrial processing peptidase (MPP) is essential for the maturation process of the proteins imported into mitochondria from cytoplasm. Cytochrome bc₁ complex is a component of the mitochondrial respiratory chain. The <font face=symbol>a</font> and <font face=symbol>b</font> subunits of MPP and the core subunits of the cytochrome bc₁ complex, UCR-1 and UCR-2, are homologous to one another. In spite of their biological importance, our knowledge about those in nematodes is very limited. C. elegans has six genes coding for proteins homologous to them. On primary structure comparison and biochemical and enzymological analyses, the gene products were assigned as follows: Y71G12B.24 (mppa-1), <font face=symbol>a</font>-MPP; ZC410.2 (mppb-1), <font face=symbol>b</font>-MPP; F56D2.1 (ucr-1), UCR-1; VW06B3R.1 (ucr-2.1), T10B10.2 (ucr-2.2); and T24C4.1 (ucr-2.3), UCR-2. The primary structures of <font face=symbol>b</font>-MPP and UCR-1 from Brugia malayi, a parasitic nematode causing human filariasis, were deduced from cDNA sequences. Phylogenetic analysis was performed on the MPP and UCR core subunits. It is thought that <font face=symbol>b</font>-MPP and UCR-1 evolved from a common ancestral molecule during molecular evolution. Interestingly, the nematode UCR-1s appear to have branched from <font face=symbol>b</font>-MPP before the separation of animals and fungi, while the mammalian UCR-1s appear to have branched after the separation of nematoda and arthropoda. Knockdown of ucr-1 by soaking RNAi caused >90% embryonic lethality. RNAi of mppb-1 or mppa-1 was >50% lethal, and combination RNAi of them was >80% lethal. Although either the single RNAi of ucr-2.1, ucr-2.2 or ucr-2.3, or the combination RNAi of any two of them caused comparatively low lethality (<30%), synthetic RNAi of all of them was >60% lethal. These results suggest the essentiality of MPP and the UCR core protein, and functional redundancy among the UCR-2 subunits. In addition, the deletion mutants mppb-1(tm1326) and ucr-1(tm1181) were both inviable or sterile. Thus MPP and the bc₁ complex are thought to be essential for viability. The orthologous proteins are presumed to be analogously essential for parasitic nematodes such as B. malayi and hence to be potential targets for anti-parasitic agents.