Document Detail


Acetate produced in the mitochondrion is the essential precursor for lipid biosynthesis in procyclic trypanosomes.
MedLine Citation:
PMID:  19625628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acetyl-CoA produced in mitochondria from carbohydrate or amino acid catabolism needs to reach the cytosol to initiate de novo synthesis of fatty acids. All eukaryotes analyzed so far use a citrate/malate shuttle to transfer acetyl group equivalents from the mitochondrial matrix to the cytosol. Here we investigate how this acetyl group transfer occurs in the procyclic life cycle stage of Trypanosoma brucei, a protozoan parasite responsible of human sleeping sickness and economically important livestock diseases. Deletion of the potential citrate lyase gene, a critical cytosolic enzyme of the citrate/malate shuttle, has no effect on de novo biosynthesis of fatty acids from (14)C-labeled glucose, indicating that another route is used for acetyl group transfer. Because acetate is produced from acetyl-CoA in the mitochondrion of this parasite, we considered genes encoding cytosolic enzymes producing acetyl-CoA from acetate. We identified an acetyl-CoA synthetase gene encoding a cytosolic enzyme (AceCS), which is essential for cell viability. Repression of AceCS by inducible RNAi results in a 20-fold reduction of (14)C-incorporation from radiolabeled glucose or acetate into de novo synthesized fatty acids. Thus, we demonstrate that the essential cytosolic enzyme AceCS of T. brucei is responsible for activation of acetate into acetyl-CoA to feed de novo biosynthesis of lipids. To date, Trypanosoma is the only known eukaryotic organism that uses acetate instead of citrate to transfer acetyl groups over the mitochondrial membrane for cytosolic lipid synthesis.
Authors:
Loïc Rivière; Patrick Moreau; Stefan Allmann; Matthias Hahn; Marc Biran; Nicolas Plazolles; Jean-Michel Franconi; Michael Boshart; Frédéric Bringaud
Related Documents :
7374368 - Inhibition of mitochondrial fatty acid elongation by antibodies to 3-ketoacyl-coa thiol...
17530838 - Discovery of potent, selective, orally bioavailable stearoyl-coa desaturase 1 inhibitors.
7174678 - Selective incorporation of polyunsaturated fatty acids into phosphatidylcholine by rat ...
7068598 - 4-bromocrotonic acid, an effective inhibitor of fatty acid oxidation and ketone body de...
3539348 - Gastric acid secretion and mucosal defense mechanisms with special reference to the rol...
3144058 - Structure-activity relationships for osteolathyrism: ii. effects of alkyl-substituted a...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-22
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  106     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-08-26     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12694-9     Citation Subset:  IM    
Affiliation:
Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, Unité Mixte de Recherche 5234 Centre National de la Recherche Scientifique, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetate-CoA Ligase / antagonists & inhibitors,  genetics,  physiology
Acetates / metabolism*
Acetyl Coenzyme A / metabolism
Animals
Citric Acid / metabolism
Lipids / biosynthesis*
Malates / metabolism
Mitochondria / metabolism*
Multienzyme Complexes / genetics,  physiology
Oxo-Acid-Lyases / genetics,  physiology
RNA Interference
Trypanosoma brucei brucei / metabolism*
Chemical
Reg. No./Substance:
0/Acetates; 0/Lipids; 0/Malates; 0/Multienzyme Complexes; 6915-15-7/malic acid; 72-89-9/Acetyl Coenzyme A; 77-92-9/Citric Acid; EC 4.1.3.-/Oxo-Acid-Lyases; EC 4.1.3.6/citrate (pro-3S)-lyase; EC 6.2.1.1/Acetate-CoA Ligase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  High-affinity lamprey VLRA and VLRB monoclonal antibodies.
Next Document:  Pharmacokinetics and Pharmacodynamics of the Urotensin-II Receptor Antagonist Palosuran in Healthy M...