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Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania
Author(s) -
Zhang Kai,
Pompey Justine M,
Hsu FongFu,
Key Phillip,
Bandhuvula Padmavathi,
Saba Julie D,
Turk John,
Beverley Stephen M
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601565
Subject(s) - biology , leishmania , sphingolipid , kinetoplastida , ethanolamine , metabolism , biochemistry , de novo synthesis , protozoal disease , parasite hosting , immunology , enzyme , malaria , world wide web , computer science
In most eukaryotes, sphingolipids (SLs) are critical membrane components and signaling molecules. However, mutants of the trypanosomatid protozoan Leishmania lacking serine palmitoyltransferase ( spt2 − ) and SLs grow well, although they are defective in stationary phase differentiation and virulence. Similar phenotypes were observed in sphingolipid (SL) mutant lacking the degradatory enzyme sphingosine 1‐phosphate lyase ( spl − ). This epistatic interaction suggested that a metabolite downstream of SLs was responsible. Here we show that unlike other organisms, the Leishmania SL pathway has evolved to be the major route for ethanolamine (EtN) synthesis, as EtN supplementation completely reversed the viability and differentiation defects of both mutants. Thus Leishmania has undergone two major metabolic shifts: first in de‐emphasizing the metabolic roles of SLs themselves in growth, signaling, and maintenance of membrane microdomains, which may arise from the unique combination of abundant parasite lipids; Second, freed of typical SL functional constraints and a lack of alternative routes to produce EtN, Leishmania redirected SL metabolism toward bulk EtN synthesis. Our results thus reveal a striking example of remodeling of the SL metabolic pathway in Leishmania .