Trypanosoma brucei; Phospholipid synthesis; Cardiolipin; Phosphatidylethanolamine; Phosphatidylserine; Eukaryotic elongation factor 1A; Protein modification; Trypanosomes; membranes; phospholipids; biosynthesis; mitochondrium; eEF1A; Lipids; Metabolism
Macêdo Juan P, Schmidt Remo S, Mäser Pascal, Rentsch Doris, Vial Henri J, Sigel Erwin, Bütikofer Peter (2013), Characterization of choline uptake in Trypanosoma brucei procyclic and bloodstream forms., in Molecular and biochemical parasitology
, 190(1), 16-22.
Jelk Jennifer, Gao Ningguo, Serricchio Mauro, Signorell Aita, Schmidt Remo S, Bangs James D, Acosta-Serrano Alvaro, Lehrman Mark A, Bütikofer Peter, Menon Anant K (2013), Glycoprotein biosynthesis in a eukaryote lacking the membrane protein Rft1., in The Journal of biological chemistry
, 288(28), 20616-23.
Huang Xiao, Jain Arjun, Baumann Marc, Körner Meike, Surbek Daniel, Bütikofer Peter, Albrecht Christiane (2013), Increased placental phospholipid levels in pre-eclamptic pregnancies., in International journal of molecular sciences
, 14(2), 3487-99.
Ramakrishnan Srinivasan, Serricchio Mauro, Striepen Boris, Bütikofer Peter (2013), Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans., in Progress in lipid research
, 52(4), 488-512.
Serricchio Mauro, Bütikofer Peter (2013), Phosphatidylglycerophosphate synthase associates with a mitochondrial inner membrane complex and is essential for growth of Trypanosoma brucei., in Molecular microbiology
, 87(3), 569-79.
Farine Luce, Bütikofer Peter (2013), The ins and outs of phosphatidylethanolamine synthesis in Trypanosoma brucei., in Biochimica et biophysica acta
, 1831(3), 533-42.
Mittal Nimisha, Subramanian Gowri, Bütikofer Peter, Madhubala Rentala (2013), Unique posttranslational modifications in eukaryotic translation factors and their roles in protozoan parasite viability and pathogenesis., in Molecular and biochemical parasitology
, 187(1), 21-31.
Serricchio Mauro, Bütikofer Peter (2012), An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote., in Proceedings of the National Academy of Sciences of the United States of America
, 109(16), E954-E961.
Greganova Eva, Bütikofer Peter (2012), Ethanolamine phosphoglycerol attachment to eEF1A is not essential for normal growth of Trypanosoma brucei., in Scientific reports
, 2, 254-254.
Eltschinger Sandra, Greganova Eva, Heller Manfred, Bütikofer Peter, Altmann Michael (2012), Eukaryotic translation elongation factor 1A (eEF1A) domain I from S. cerevisiae is required but not sufficient for inter-species complementation., in PloS one
, 7(7), 42338-42338.
Gonzalez-Salgado Amaia, Steinmann Michael E, Greganova Eva, Rauch Monika, Mäser Pascal, Sigel Erwin, Bütikofer Peter (2012), myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei., in The Journal of Biological Chemistry
, 287(16), 13313-23.
Serricchio Mauro, Bütikofer Peter (2011), Trypanosoma brucei: a model micro-organism to study eukaryotic phospholipid biosynthesis, in FEBS J.
, 278, 1035-1046.
Greganova Eva, Altmann Michael, Bütikofer Peter (2011), Unique modifications of translation elongation factors., in The FEBS Journal
, 278(15), 2613-24.
Greganova Eva, Heller Manfred, Bütikofer Peter (2010), A structural domain mediates attachment of ethanolamine phosphoglycerol to eukaryotic elongation factor 1A in Trypanosoma brucei., in PloS one
, 5(3), 9486-9486.
Smith Terry K, Bütikofer Peter (2010), Lipid metabolism in Trypanosoma brucei., in Molecular and biochemical parasitology
, 172(2), 66-79.
Bütikofer Peter, Greganova Eva, Liu Yuk-Chien, Edwards Ian J, Lehane Michael J, Acosta-Serrano Alvaro (2010), Lipid remodelling of glycosylphosphatidylinositol (GPI) glycoconjugates in procyclic-form trypanosomes: biosynthesis and processing of GPIs revisited., in The Biochemical journal
, 428(3), 409-18.
African trypanosomes are protozoan parasites causing human African sleeping sickness and a related disease, nagana, in animals. Despite the devastating impact of the diseases on human and animal health in rural sub-Saharan Africa, research on trypanosomes has received little recognition among the scientific community for decades. However, the discovery of several important biological phenomena in trypanosomes, such as RNA editing, trans-splicing, glycosylphosphatidylinositol-anchoring and antigenic variation, which were subsequently found to occur in other eukaryotic organisms as well, has changed the attitude towards trypanosomes and they have become a valuable model organism to study basic questions in biology.Because African trypanosomes are human and animal pathogens, research on trypanosomes has often focused on identifying cellular and metabolic events that may have the potential to become drug targets to inhibit parasite proliferation. We decided to focus our research on two aspects in trypanosome biology that have received little attention in the past, the modification of eukaryotic elongation factor 1A (eEF1A) by ethanolamine phosphoglycerol (EPG) and the metabolism of phospholipids in Trypanosoma brucei. Although EPG modification of eEF1A has been discovered more than two decades ago, the pathway for EPG synthesis and attachment to protein, and its functional significance, have remained elusive. We plan to address these questions by introducing eEF1A constructs, containing amino acid point mutations or deletions, into T. brucei procyclic forms to study functional complementation of these mutant proteins and their interactions with other cellular components. In addition, since we recently demonstrated a direct link between EPG modification and phospholipid metabolism, by showing that the ethanolamine moiety of EPG derives from the phospholipid, phosphatidylethanolamine, we plan to identify and characterize selected metabolic pathways involved in phospholipid synthesis in T. brucei. Based on our previously published observation that the parasite mitochondrium is particularly sensitive to changes in lipid composition, we will focus on characterizing the reactions involved in the biosynthesis of cardiolipin, a characteristic and functionally important phospholipid in mitochondria. Our preliminary observation that one reaction in the synthesis of cardiolipin in T. brucei may involve the action of a bacterial-type, rather than eukaryotic-type, enzyme offers the possibility that this pathway may represent a potential drug target against trypanosomes. In addition, since alterations in membrane lipid composition, induced by experimentally interfering with biosynthetic pathways, are expected to cause pleiotropic or lethal effects in T. brucei, our studies will contribute to a better understanding of the general roles of phospholipids in eukaryotes.Together, our studies have the potential to reveal unique, i.e. parasite-specific, pathways for phospholipid synthesis and turnover in T. brucei and, in addition, shed light on the biosynthesis and function of the EPG modification of eEF1A in a eukaryotic model organism.