Glucose-induced remodeling of intermediary and energy metabolism in procyclic Trypanosoma brucei.
The procyclic form of Trypanosoma brucei is a parasitic protozoan that normally dwells in the midgut of its insect vector. In vitro, this parasite prefers d-glucose to l -proline as a carbon source, although this amino acid is the main carbon source available in its natural habitat. Here, we investigated how l -proline is metabolized in glucose-rich and glucose-depleted conditions. Analysis of the excreted end products of (13)C-enriched l -proline metabolism showed that the amino acid is converted into succinate or l -alanine depending on the presence or absence of d-glucose, respectively. The fact that the pathway of l -proline metabolism was truncated in glucose-rich conditions was confirmed by the analysis of 13 separate RNA interference-harboring or knock-out cell lines affecting different steps of this pathway. For instance, RNA interference studies revealed the loss of succinate dehydrogenase activity to be conditionally lethal only in the absence of d-glucose, confirming that in glucose-depleted conditions, l -proline needs to be converted beyond succinate. In addition, depletion of the F(0)/F(1)-ATP synthase activity by RNA interference led to cell death in glucose-depleted medium, but not in glucose-rich medium. This implies that, in the presence of d-glucose, the importance of the F(0)/F(1)-ATP synthase is diminished and ATP is produced by substrate level phosphorylation. We conclude that trypanosomes develop an elaborate adaptation of their energy production pathways in response to carbon source availability.
Coustou
Virginie
V
Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, UMR-5234 CNRS.
Biran
Marc
M
Breton
Marc
M
Guegan
Fabien
F
Rivière
Loïc
L
Plazolles
Nicolas
N
Nolan
Derek
D
Barrett
Michael P
MP
Franconi
Jean-Michel
JM
Bringaud
Frédéric
F
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002244:Carbon / Q000737:chemistry; D003470:Culture Media / Q000737:chemistry; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry; D006180:Proton-Translocating ATPases / Q000378:metabolism; D034622:RNA Interference; D014346:Trypanosoma brucei brucei / Q000378:metabolism* / Q000502:physiology*
D003470:Culture Media; D000105:Acetyl Coenzyme A; D002244:Carbon; D000255:Adenosine Triphosphate; D011392:Proline; D006180:Proton-Translocating ATPases; D005947:Glucose