|
| Status |
Public on Aug 01, 2014 |
| Title |
Gene expression analysis of a double knockout of TCA cycle enzymes IDH and KDH |
| Organism |
Plasmodium falciparum |
| Experiment type |
Expression profiling by array
|
| Summary |
New antimalarial drugs are urgently needed to control drug resistant forms of the malaria parasite, Plasmodium falciparum. Although mitochondrial metabolism is the target of both existing drugs and new lead compounds, the role of the mitochondrial tricarboxylic acid (TCA) cycle remains poorly understood. Herein, we describe 11 genetic knockout parasite lines that delete six of the eight TCA cycle enzymes. Although all TCA knockouts grew normally in asexual blood stages, these metabolic deficiencies halted lifecycle progression in later stages. Specifically, aconitase knockout parasites arrested as late gametocytes, whereas α-ketoglutarate dehydrogenase deficient parasites failed to develop oocysts in the mosquitoes. Mass-spectrometry analysis of 13C isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development .
|
| |
|
| Overall design |
Two parallel timecourses resulting in a total of 16 samples (8 wildtype, Isocitrate Dehydrogenase/alpha-Ketogluterate Dehydrogenase double knockout) were hybridized against a Cy3-labeled reference pool of 3D7 mixed stage parasites on a two-color array.
|
| |
|
| Contributor(s) |
Ke H, Lewis IA, Morrisey JM, McLean KJ, Ganesan SM, Painter HJ, Mather MW, Jacobs-Lorena M, Llinás M, Vaidya AB |
| Citation(s) |
25843709 |
| |
| Submission date |
Jul 02, 2014 |
| Last update date |
Jul 31, 2019 |
| Contact name |
Heather J Painter |
| E-mail(s) |
hjp117@psu.edu
|
| Phone |
8148673527
|
| Organization name |
Penn State University
|
| Department |
Biochemistry and Molecular Biology
|
| Lab |
Manuel Llinas
|
| Street address |
Millennium Science Center
|
| City |
University Park |
| State/province |
Pennsylvania |
| ZIP/Postal code |
16802 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17880 |
Agilent-032491 3D7v7.1_transcriptome |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA254114 |
Less...
More...