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Mitochondrial drug targets in apicomplexan parasites
Michael W Mather1, Karl W Henry, Akhil B Vaidya
1Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129, USA.
Current Drug Targets
|February 3, 2007
Summary
Mitochondria in apicomplexan parasites have minimal genomes and are crucial drug targets. Understanding their unique functions, like iron-sulfur cluster assembly, aids in developing new antiparasitic therapies.
Area of Science:
- Parasitology
- Mitochondrial Biology
- Drug Discovery
Background:
- Mitochondria in apicomplexan parasites exhibit highly reduced genomes, encoding only three proteins.
- The genus Cryptosporidium even lacks a mitochondrial genome entirely, suggesting evolutionary reduction.
- Mitochondrial physiology presents viable targets for antiparasitic drug development.
Purpose of the Study:
- To explore the unique features of apicomplexan mitochondria.
- To identify potential antiparasitic drug targets within mitochondrial pathways.
- To understand the mechanism of action of drugs like atovaquone.
Main Methods:
- Analysis of mitochondrial genome content and evolutionary reduction.
- Investigation of mitochondrial electron transport and membrane potential.
- Genome sequence analyses to identify nuclear-encoded mitochondrial components.
Main Results:
- Mitochondria, despite reduced genomes, perform essential functions beyond ATP production, such as iron-sulfur cluster assembly.
- Atovaquone selectively inhibits the cytochrome bc(1) complex, collapsing mitochondrial membrane potential.
- Unusual components of the mitochondrial replication, repair, and expression machinery are being identified.
Conclusions:
- Apicomplexan mitochondria, though reduced, are critical for parasite survival and represent promising targets for novel antiparasitic drugs.
- Understanding the specific metabolic roles and unique molecular machinery of these mitochondria can guide drug discovery efforts.
- Targeting mitochondrial functions offers a strategy for developing new therapies against parasitic infections.
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