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Journal article
The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in Plasmodium falciparum
The Journal of biological chemistry, v 293(21), pp 8128-8137
25 May 2018
PMID: 29626096
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The phylum Apicomplexa contains a group of protozoa causing diseases in humans and livestock. Plasmodium spp., the causative agent of malaria, contains a mitochondrion that is very divergent from that of their hosts. The malarial mitochondrion is a clinically validated target for the antimalarial drug atovaquone, which specifically blocks the electron transfer activity of the bc(1) complex of the mitochondrial electron transport chain (mtETC). Most mtETC proteins are nuclear-encoded and imported from the cytosol, but three key protein subunits are encoded in the Plasmodium mitochondrial genome: cyt b, COXI, and COXIII. They are translated inside the mitochondrion by mitochondrial ribosomes (mitoribosomes). Here, we characterize the function of one large mitoribosomal protein in Plasmodium falciparum, PfmRPL13. We found that PfmRPL13 localizes to the parasite mitochondrion and is refractory to genetic knockout. Ablation of PfmRPL13 using a conditional knockdown system (TetR-DOZI-aptamer) caused a series of adverse events in the parasite, including mtETC deficiency, loss of mitochondrial membrane potential ((m)), and death. The PfmRPL13 knockdown parasite also became hypersensitive to proguanil, a drug proposed to target an alternative process for maintaining (m). Surprisingly, transmission EM revealed that PfmRPL13 disruption also resulted in an unusually elongated and branched mitochondrion. The growth arrest of the knockdown parasite could be rescued with a second copy of PfmRPL13, but not by supplementation with decylubiquinone or addition of a yeast dihydroorotate dehydrogenase gene. In summary, we provide first and direct evidence that mitoribosomes are essential for malaria parasites to maintain the structural and functional integrity of the mitochondrion.
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Details
- Title
- The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in Plasmodium falciparum
- Creators
- Hangjun Ke - Drexel UniversitySwati Dass - Drexel UniversityJoanne M. Morrisey - Drexel UniversityMichael W. Mather - Drexel UniversityAkhil B. Vaidya - Drexel University
- Publication Details
- The Journal of biological chemistry, v 293(21), pp 8128-8137
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 10
- Grant note
- R01 AI028398 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA K22AI127702 / National Institutes of Health Career Transition Award K22; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AI028398 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000433224600018
- Scopus ID
- 2-s2.0-85047909357
- Other Identifier
- 991019168253204721
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- Web of Science research areas
- Biochemistry & Molecular Biology