期刊
CURRENT DRUG TARGETS
卷 8, 期 1, 页码 49-60出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138945007779315632
关键词
apicomplexan parasites; Plasmodium; Theileria; Toxoplasma; Cryptosporidium; mitochondrial DNA; ubiquinone; atovaquone; ubiquinone-linked dehydrogenases; electron transport chain; iron-sulfur cluster biosynthesis; mitochondrial carriers
资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI053148, R01AI028398, R56AI028398, R22AI028398, Z01AI005093] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI05093, AI053148, R01 AI028398, AI028398] Funding Source: Medline
In evolutionary terms, mitochondria in apicomplexan parasites appear to be relicts-in-the-making: they possess the smallest mitochondrial genomes known, encoding only three proteins, and in one genus, Oyptosporidium, the genome is eliminated altogether. Several features of mitochondrial physiology provide validated or potential targets for antiparasitic drugs. Atovaquone, a broad spectrum antiparasitic drug, selectively inhibits mitochondrial electron transport at the cytochrome bc(1) complex and collapses mitochondrial membrane potential. Recent investigations using model systems provide important insights into the mechanism of action for this drug, which may prove valuable for development of other selective inhibitors of mitochondrial electron transport. Although mitochondria do not appear to be a source of ATP during the erythrocytic stages in Plasmodium species, they do serve other critical functions, including the assembly of iron-sulfur clusters and various other biosynthetic processes depending on the species. To serve these metabolic functions, parasites need to maintain the apparatus for mitochondrial genome replication, repair, recombination, transcription, and translation, components of which are encoded in the nucleus and imported into the mitochondrion. Several unusual aspects of the components of this apparatus are coming to light through genome sequence analyses, and could provide potential targets for antiparasitic drug discovery and development.
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