Mitochondrial function in Babesia bovis

• Published in: International journal for parasitology Vol. 22; no. 2; pp. 165 - 171
• Main Authors: Gozar, M.M.G, O'Sullivan, W.J, Bagnara, A.S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.04.1992
• Subjects: adenosinetriphosphatase; Animals; atp-adp translocase; Babesia bovis; Babesia bovis - drug effects; Babesia bovis - ultrastructure; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; biosynthesis; electron transfer; electron transport chain; enzyme inhibitors; enzymes; Fundamental and applied biological sciences. Psychology; inhibition; Invertebrates; metabolic inhibitors; mitochondria; Mitochondria - drug effects; Mitochondria - physiology; protein synthesis; proton pump; Protozoa; pyrimidines; ubiquinones; Protozoa; Respiratory chain; Mitochondria; Energy metabolism; Radiolabelling; Parasite; Biosynthesis; Inhibitor; Babesia bovis; Sporozoa; Chromatography; Pyrimidine
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/0020-7519(92)90097-5

A variety of anti-mitochondrial drugs that had previously been found to inhibit the growth of the malarial parasite Plasmodium falciparum were tested on Babesia bovis in vitro. Several of these drugs were found to be non-toxic towards B. bovis. However, those drugs that were found to inhibit babesial growth included compounds (shown in parentheses) that have the following putative mitochondrial targets in the parasite: ATP synthetase complex (rhodamine 123, oligomycin, Janus Green); ATP-ADP translocase (bongkrekic acid); electron transport (rotenone, n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), antimycin A); ubiquinone (CoQ) function (BW58C, menoctone); protein synthesis (tetracycline); and the proton pump (CCCP). We have also investigated the effects of some of these drugs on pyrimidine biosynthesis de novo by following the incorporation of [14C]bicarbonate into pyrimidine nucleotides and into the pyrimidine moieties of nucleic acids. The ubiquinone analogues BW58C and menoctone inhibited this pathway in the nm-micromolar range of concentrations. Inhibitors of electron transport (antimycin A and oligomycin) and an uncoupler (CCCP) were also effective inhibitors of pyrimidine biosynthesis de novo. We conclude that B. bovis has a functional mitochondrion that contributes significantly to pyrimidine biosynthesis de novo and to the overall energy metabolism of the parasite.