Journal article
ATP Synthase Complex of Plasmodium falciparum: DIMERIC ASSEMBLY IN MITOCHONDRIAL MEMBRANES AND RESISTANCE TO GENETIC DISRUPTION
The Journal of biological chemistry, v 286(48), pp 41312-41322
02 Dec 2011
PMID: 21984828
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background:
The role of ATP synthase in blood stages of malaria parasites has been unclear.
Results:
Canonical subunits were targeted to the mitochondrion, could not be deleted by gene disruption, and were present in large complexes.
Conclusion:
Plasmodium
ATP synthase is likely essential and forms a dimeric complex.
Significance
Composition, properties, structure, and drugability of the complex should be fully investigated.
The rotary nanomotor ATP synthase is a central player in the bioenergetics of most organisms. Yet the role of ATP synthase in malaria parasites has remained unclear, as blood stages of
Plasmodium falciparum
appear to derive ATP largely through glycolysis. Also, genes for essential subunits of the F
O
sector of the complex could not be detected in the parasite genomes. Here, we have used molecular genetic and immunological tools to investigate the localization, complex formation, and functional significance of predicted ATP synthase subunits in
P. falciparum
. We generated transgenic
P. falciparum
lines expressing seven epitope-tagged canonical ATP synthase subunits, revealing localization of all but one of the subunits to the mitochondrion. Blue native gel electrophoresis of
P. falciparum
mitochondrial membranes suggested the molecular mass of the ATP synthase complex to be greater than 1 million daltons. This size is consistent with the complex being assembled as a dimer in a manner similar to the complexes observed in other eukaryotic organisms. This observation also suggests the presence of previously unknown subunits in addition to the canonical subunits in
P. falciparum
ATP synthase complex. Our attempts to disrupt genes encoding β and γ subunits were unsuccessful, suggesting an essential role played by the ATP synthase complex in blood stages of
P. falciparum
. These studies suggest that, despite some unconventional features and its minimal contribution to ATP synthesis,
P. falciparum
ATP synthase is localized to the parasite mitochondrion, assembled as a large dimeric complex, and is likely essential for parasite survival.
Metrics
Details
- Title
- ATP Synthase Complex of Plasmodium falciparum
- Creators
- Praveen Balabaskaran Nina - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Joanne M Morrisey - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Suresh M Ganesan - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Hangjun Ke - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129April M Pershing - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Michael W Mather - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Akhil B Vaidya - From the Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129
- Publication Details
- The Journal of biological chemistry, v 286(48), pp 41312-41322
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- AI28398 / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000298057500018
- Scopus ID
- 2-s2.0-82355181574
- Other Identifier
- 991014878321104721
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- Web of Science research areas
- Biochemistry & Molecular Biology