title: Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation.
abstract: Autophagy is a conserved cellular process to degrade and recycle cytoplasmic components. During autophagy, lysosomes fuse with an autophagosome to form an autolysosome. Sequestered components are degraded by lysosomal hydrolases and presumably released into the cytosol by lysosomal efflux permeases. Following starvation-induced autophagy, lysosome homeostasis is restored by autophagic lysosome reformation (ALR) requiring activation of the "target of rapamycin" (TOR) kinase. Spinster (Spin) encodes a putative lysosomal efflux permease with the hallmarks of a sugar transporter. Drosophila spin mutants accumulate lysosomal carbohydrates and enlarged lysosomes. Here we show that defects in spin lead to the accumulation of enlarged autolysosomes. We find that spin is essential for mTOR reactivation and lysosome reformation following prolonged starvation. Further, we demonstrate that the sugar transporter activity of Spin is essential for ALR.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Yueguang
authors.initials: Y
authors.lastname: Rong
authors.forename: Christina K
authors.initials: CK
authors.lastname: McPhee
authors.forename: Christina
authors.initials: C
authors.lastname: McPhee
authors.forename: Shuangshen
authors.initials: S
authors.lastname: Deng
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Lilian
authors.initials: L
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Kirsten
authors.initials: K
authors.lastname: Tracy
authors.forename: Eric H
authors.initials: EH
authors.lastname: Baehrecke
authors.forename: Eric H
authors.initials: EH
authors.lastname: Baehreck
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001483:Base Sequence; D050260:Carbohydrate Metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D034622:RNA Interference; D051381:Rats; D017386:Sequence Homology, Amino Acid; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D052118:Lysosomal-Associated Membrane Protein 1; D008565:Membrane Proteins; C429164:spin protein, Drosophila; D058570:TOR Serine-Threonine Kinases