ATP-driven and AMPK-independent autophagy in an early branching eukaryotic parasite

Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabol...

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Bibliographic Details
Published in:Autophagy 2017-04, Vol.13 (4), p.715-729
Main Authors: Li, Feng-Jun, Xu, Zhi-Shen, Soo, Andy D. S., Lun, Zhao-Rong, He, Cynthia Y.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
amino acid starvation
Amino Acids - deficiency
AMP-Activated Protein Kinases - metabolism
AMPK
Animals
Autophagosomes - drug effects
Autophagosomes - metabolism
autophagy
Autophagy - drug effects
Basic Research Paper
cell respiration
Energy Metabolism - drug effects
Glucose - metabolism
glycolysis
Life Cycle Stages
Parasites - cytology
Parasites - drug effects
Parasites - enzymology
Proline - metabolism
Trypanosoma brucei
Trypanosoma brucei brucei - cytology
Trypanosoma brucei brucei - drug effects
Trypanosoma brucei brucei - enzymology
Trypanosoma brucei brucei - growth & development
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Summary:Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabolic stimuli to initiate autophagy in higher eukaryotes. In the early-branching unicellular parasite Trypanosoma brucei, which can proliferate as procyclic form (PCF) in the tsetse fly or as bloodstream form (BSF) in animal hosts, autophagy is robustly triggered by amino acid deficiency but not by glucose depletion. Taking advantage of the clearly defined adenosine triphosphate (ATP) production pathways in T. brucei, we have shown that autophagic activity depends on the levels of cellular ATP production, using either glucose or proline as a carbon source. While autophagosome formation positively correlates with cellular ATP levels; perturbation of ATP production by removing carbon sources or genetic silencing of enzymes involved in ATP generation pathways, also inhibited autophagy. This obligate energy dependence and the lack of glucose starvation-induced autophagy in T. brucei may reflect an adaptation to its specialized, parasitic life style.
ISSN:1554-8627
1554-8635
DOI:10.1080/15548627.2017.1280218