title: Acidocalcisome is required for autophagy in Trypanosoma brucei.
abstract: Lysosomes play important roles in autophagy, not only in autophagosome degradation, but also in autophagy initiation. In Trypanosoma brucei, an early divergent protozoan parasite, we discovered a previously unappreciated function of the acidocalcisome, a lysosome-related organelle characterized by acidic pH and large content of Ca(2+) and polyphosphates, in autophagy regulation. Starvation- and chemical-induced autophagy is accompanied with acidocalcisome acidification, and blocking the acidification completely inhibits autophagosome formation. Blocking acidocalcisome biogenesis by depleting the adaptor protein-3 complex, which does not affect lysosome biogenesis or function, also inhibits autophagy. Overall, our results support the role of the acidocalcisome, a conserved organelle from bacteria to human, as a relevant regulator in autophagy.
authors.affiliation: a Department of Biological Sciences ; National University of Singapore ; Singapore.
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Li
authors.forename: Cynthia Y
authors.initials: CY
authors.lastname: He
mesh_terms: D001343:Autophagy; D002118:Calcium / Q000737:chemistry; D002738:Chloroquine / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008985:Monensin / Q000737:chemistry; D015388:Organelles / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry; D015800:Protozoan Proteins / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: D018942:Macrolides; D010710:Phosphates; D015800:Protozoan Proteins; D002738:Chloroquine; C040929:bafilomycin A1; D008985:Monensin; D002118:Calcium
keywords: AO, acridine orange; AP-3, adaptor protein-3; ATG, autophagy-related; BODIPY-CQ, BODIPY-chloroquine; BafA1, bafilomycin A1; CQ, chloroquine; DAPI, 4′, 6-diamidino-2-phenylindole; MTORC1, mechanistic target of rapamycin complex 1; PPi, pyrophosphate; PtdIns3K, phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol 3-phosphate; RNAi, RNA interference; T. brucei, Trypanosoma brucei; TOR, target of rapamycin; TbVMA1, the subunit A of V-H+-ATPase in Trypanosoma brucei; TbVP1, vacuolar pyrophosphatase in Trypanosoma brucei; TbVPH1, the α, subunit of V-H+-ATPase in Trypanosoma brucei; Tbβ3, the β3 subunit of adaptor protein-3 complex in Trypanosoma brucei; Tbδ, the δ, subunit of adaptor protein-3 complex in Trypanosoma brucei; Trypanosoma brucei; V-H+-ATPase, vacuolar-type H+-ATPase; V-PPase, vacuolar pyrophophatase; acidity; acidocalcisome; autophagy; coumarin-CQ, coumarin-chloroquine; lysosome-related organelle; polyP, polyphosphate; protozoan parasite