Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei
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Phosphatidylethanolamine (PE) and phosphatidylserine (PS) are ubiquitously expressed and metabolically interconnected glycerophospholipids in eukaryotes and prokaryotes. In Trypanosoma brucei, PE synthesis has been shown to occur mainly via the Kennedy pathway, one of the three routes leading to PE synthesis in eukaryotes, while PS synthesis has not been studied experimentally. We now reveal the importance of T. brucei PS synthase 2 (TbPSS2) and T. brucei PS decarboxylase (TbPSD), two key enzymes involved in aminophospholipid synthesis, for trypanosome viability. By using tetracycline-inducible down-regulation of gene expression and in vivo and in vitro metabolic labeling, we found that TbPSS2 i) is necessary for normal growth of procyclic trypanosomes, ii) localizes to the endoplasmic reticulum and iii) represents the unique route for PS formation in T. brucei. In addition, we identified TbPSD as type I PS decarboxylase in the mitochondrion and found that it is processed proteolytically at a WGSS cleavage site into a heterodimer. Down-regulation of TbPSD expression affected mitochondrial integrity in both procyclic and bloodstream form trypanosomes, decreased ATP production via oxidative phosphorylation in procyclic form and affected parasite growth.
Farine , L , Jelk , J , Choi , J-Y , Voelker , D R , Nunes , J , Smith , T K & Bütikofer , P 2017 , ' Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei ' Molecular Microbiology , vol 104 , no. 3 , pp. 412-427 . DOI: 10.1111/mmi.13637
Copyright 2017 The Authors Molecular Microbiology Published by John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The work was supported by Swiss National Science Foundation grant 149353 to PB, Wellcome Trust grants 067441 and 093228 and European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED) to TKS, and National Institutes of Health grants NIAID AI 097218 and NIGMS GM 104485 to DRV.
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