Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Stephens, Jennifer L.; Lee, Soo Hee; Paul, Kimberly S.; Englund, Paul T.

doi:10.1074/jbc.m609037200

Cited by 94 publications

(119 citation statements)

References 69 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…To (41,42). In line with these reports, we found that in TbCls-knockout parasites incubated in the presence of tetracycline, radioactivity was incorporated into all major glycerophospholipid classes (Fig.…”

Section: Resultssupporting

confidence: 86%

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Serricchio

Bütikofer

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cardiolipin is important for bacterial and mitochondrial stability and function. The final step in cardiolipin biosynthesis is catalyzed by cardiolipin synthase and differs mechanistically between prokaryotes and eukaryotes. To study the importance of cardiolipin synthesis for mitochondrial integrity, membrane protein complex formation, and cell proliferation in the human and animal pathogenic protozoan parasite, Trypanosoma brucei , we generated conditional cardiolipin synthase-knockout parasites. We found that cardiolipin formation in T. brucei procyclic forms is catalyzed by a bacterial-type cardiolipin synthase, providing experimental evidence for a prokaryotic-type cardiolipin synthase in a eukaryotic organism. Ablation of enzyme expression resulted in inhibition of de novo cardiolipin synthesis, reduction in cellular cardiolipin levels, alterations in mitochondrial morphology and function, and parasite death in culture. By using immunofluorescence microscopy and blue-native gel electrophoresis, cardiolipin synthase was shown to colocalize with inner mitochondrial membrane proteins and to be part of a large protein complex. During depletion of cardiolipin synthase, the levels of cytochrome oxidase subunit IV and cytochrome c1, reflecting mitochondrial respiratory complexes IV and III, respectively, decreased progressively.

show abstract

Section: Resultssupporting

confidence: 86%

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Serricchio

Bütikofer

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Antiserum specific for lipoylated proteins recognizes a single 40-kDa protein in this stage as well as in procyclic-form parasites (219). As observed in T. gondii, the type II FAS protein ACP is required for proper lipoylation, indicating that lipoate synthesis is responsible for lipoylating the 40-kDa protein.…”

Section: Lipoylated Complexes In Kinetoplastidsmentioning

confidence: 66%

Lipoic Acid Metabolism in Microbial Pathogens

Spalding

Prigge

2010

Microbiol Mol Biol Rev

164

204

View full text Add to dashboard Cite

SUMMARY Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.

show abstract

“…This modification occurs at, or near, the site of PE synthesis and temporarily renders eEF1A membrane-bound. Interestingly, plant eEF1A has been reported to incorporate 14 C-labeled fatty acids, however, no direct evidence was provided that eEF1A was modified with an entire PE molecule (11 (49), showed no incorporation of radioactivity into eEF1A (results not shown). However, this is not surprising, because we were unable to detect a PE-modified form of eEF1A by mass spectrometry, and, thus, this form may represent a minor fraction of total eEF1A only.…”

Section: Discussionmentioning

confidence: 95%

Phosphatidylethanolamine Is the Precursor of the Ethanolamine Phosphoglycerol Moiety Bound to Eukaryotic Elongation Factor 1A

Signorell

Jelk

Rauch

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

In addition to its conventional role during protein synthesis, eukaryotic elongation factor 1A is involved in other cellular processes. Several regions of interaction between eukaryotic elongation factor 1A and the translational apparatus or the cytoskeleton have been identified, yet the roles of the different post-translational modifications of eukaryotic elongation factor 1A are completely unknown. One amino acid modification, which so far has only been found in eukaryotic elongation factor 1A, consists of ethanolamine-phosphoglycerol attached to two glutamate residues that are conserved between mammals and plants. We now report that ethanolamine-phosphoglycerol is also present in eukaryotic elongation factor 1A of the protozoan parasite Trypanosoma brucei, indicating that this unique protein modification is of ancient origin. In addition, using RNA-mediated gene silencing against enzymes of the Kennedy pathway, we demonstrate that phosphatidylethanolamine is a direct precursor of the ethanolamine-phosphoglycerol moiety. Down-regulation of the expression of ethanolamine kinase and ethanolamine-phosphate cytidylyltransferase results in inhibition of phosphatidylethanolamine synthesis in T. brucei procyclic forms and, concomitantly, in a block in glycosylphosphatidylinositol attachment to procyclins and ethanolamine-phosphoglycerol modification of eukaryotic elongation factor 1A.

show abstract

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Cited by 94 publications

References 69 publications

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Lipoic Acid Metabolism in Microbial Pathogens

Phosphatidylethanolamine Is the Precursor of the Ethanolamine Phosphoglycerol Moiety Bound to Eukaryotic Elongation Factor 1A

Contact Info

Product

Resources

About