Many effective anthelminthics inhibit muscle contraction, either by directly interfering with processes at the neuromuscular junction or inhibiting energy metabolism. Since the mitochondrial metabolism of many parasitic helminths is predominantly anaerobic and differs substantially from that of the host, it is a potential site for chemotherapeutic attack. During the previous grant period, a number of important insights into the regulation of the enzymes involved in the mitochondrial metabolism of the parasitic nematode, Ascaris suum, have been described. The present study is designed to extend these studies and concentrate on differences that have been identified between host and parasite. Specifically, a novel component of the ascarid pyruvate dehydrogenase complex (PDC) will be further characterized and its role and that of E2 acetylation in the regulation of PDC activity by its associated kinase and phosphatase will be identified. In addition, the regulation of NADH-dependent 2-methyl branched-chain enoyl CoA reduction will be characterized using submitochondrial particles and purified ascarid enzymes, and the generation of a proton-gradient and ADP phosphorylation measured directly. Since Ca++ appears to play a unique role in the regulation of ascarid mitochondrial metabolism, Ca++ fluxes in isolated ascarid mitochondria will be measured and correlated with end-product formation and energy- generation. Preliminary experiments have suggested that mitochondrial volume is an important regulator of organic acid formation in these isolated mitochondria so that its role also will be described. These studies will permit the development of well characterized preparations of ascarid mitochondria, capable of volatile organic acid synthesis at physiological levels, and should provide a much clearer picture of energy-generation in these often studied, but still poorly understood organelles. Since these mitochondria are often used to screen compounds for potential anthelminthic activity, a clear understanding of their function is essential to intercept results meaningfully, especially since they differ so profoundly from the corresponding mammalian organelles.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Toledo
Schools of Arts and Sciences
United States
Zip Code
Geng, Jinming; Plenefisch, John; Komuniecki, Patricia R et al. (2002) Secretion of a novel developmentally regulated chitinase (family 19 glycosyl hydrolase) into the perivitelline fluid of the parasitic nematode, Ascaris suum. Mol Biochem Parasitol 124:11-21
Huang, Xinyan; Xiao, Hong; Rex, Elizabeth B et al. (2002) Functional characterization of alternatively spliced 5-HT2 receptor isoforms from the pharynx and muscle of the parasitic nematode, Ascaris suum. J Neurochem 83:249-58
Duran, E; Walker, D J; Johnson, K R et al. (1998) Developmental and tissue-specific expression of 2-methyl branched-chain enoyl CoA reductase isoforms in the parasitic nematode, Ascaris suum. Mol Biochem Parasitol 91:307-18
Mei, B; Kennedy, M W; Beauchamp, J et al. (1997) Secretion of a novel, developmentally regulated fatty acid-binding protein into the perivitelline fluid of the parasitic nematode, Ascaris suum. J Biol Chem 272:9933-41
Mei, B; Komuniecki, R; Komuniecki, P R (1997) Localization of cytochrome oxidase and the 2-methyl branched-chain enoyl CoA reductase in muscle and hypodermis of Ascaris suum larvae and adults. J Parasitol 83:760-3
Anderson, T J; Komuniecki, R; Komuniecki, P R et al. (1995) Are mitochondria inherited paternally in Ascaris? Int J Parasitol 25:1001-4
Song, H; Komuniecki, R (1994) Novel regulation of pyruvate dehydrogenase phosphatase purified from anaerobic muscle mitochondria of the adult parasitic nematode, Ascaris suum. J Biol Chem 269:31573-8
Diaz, F; Komuniecki, R W (1994) Pyruvate dehydrogenase complexes from the equine nematode, Parascaris equorum, and the canine cestode, Dipylidium caninum, helminths exhibiting anaerobic mitochondrial metabolism. Mol Biochem Parasitol 67:289-99
Duran, E; Komuniecki, R W; Komuniecki, P R et al. (1993) Characterization of cDNA clones for the 2-methyl branched-chain enoyl-CoA reductase. An enzyme involved in branched-chain fatty acid synthesis in anaerobic mitochondria of the parasitic nematode Ascaris suum. J Biol Chem 268:22391-6
Komuniecki, P R; Johnson, J; Kamhawi, M et al. (1993) Mitochondrial heterogeneity in the parasitic nematode, Ascaris suum. Exp Parasitol 76:424-37

Showing the most recent 10 out of 22 publications