title: ATP-driven and AMPK-independent autophagy in an early branching eukaryotic parasite.
abstract: 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.
authors.affiliation: a Department of Biological Sciences , National University of Singapore , Singapore.
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Li
authors.affiliation: b State Key Laboratory of Biocontrol, School of Life Sciences, and Key Laboratory of Tropical Diseases and Control of the Ministry of Education , Zhongshan Medical School, Sun Yat-Sen University , Guangzhou , China.
authors.forename: Zhi-Shen
authors.initials: ZS
authors.lastname: Xu
authors.affiliation: a Department of Biological Sciences , National University of Singapore , Singapore.
authors.forename: Andy D S
authors.initials: AD
authors.lastname: Soo
authors.affiliation: b State Key Laboratory of Biocontrol, School of Life Sciences, and Key Laboratory of Tropical Diseases and Control of the Ministry of Education , Zhongshan Medical School, Sun Yat-Sen University , Guangzhou , China.
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
authors.affiliation: a Department of Biological Sciences , National University of Singapore , Singapore.|c Centre for BioImaging Sciences , National University of Singapore , Singapore.
authors.forename: Cynthia Y
authors.initials: CY
authors.lastname: He
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000596:Amino Acids / Q000172:deficiency; D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D008018:Life Cycle Stages; D010271:Parasites / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D011392:Proline / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development
chemical_list: D000596:Amino Acids; D000255:Adenosine Triphosphate; D011392:Proline; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; Trypanosoma brucei; amino acid starvation; autophagy; cell respiration; glycolysis