title: WIPI β-propellers in autophagy-related diseases and longevity.
abstract: Autophagy is a catabolic pathway in which the cell sequesters cytoplasmic material, including long-lived proteins, lipids and organelles, in specialized double-membrane vesicles, called autophagosomes. Subsequently, autophagosomes communicate with the lysosomal compartment and acquire acidic hydrolases for final cargo degradation. This process of partial self-eating secures the survival of eukaryotic cells during starvation periods and is critically regulated by mTORC1 (mammalian target of rapamycin complex 1). Under nutrient-poor conditions, inhibited mTORC1 permits localized PtdIns(3)P production at particular membranes that contribute to autophagosome formation. Members of the human WIPI (WD-repeat protein interacting with phosphoinositides) family fulfil an essential role as PtdIns(3)P effectors at the initiation step of autophagosome formation. In the present article, we discuss the role of human WIPIs in autophagy, and the identification of evolutionarily conserved amino acids of WIPI-1 that confer PtdIns(3)P binding downstream of mTORC1 inhibition. We also discuss the PtdIns(3)P effector function of WIPIs in the context of longevity and autophagy-related human diseases, such as cancer and neurodegeneration.
authors.affiliation: Autophagy Laboratory, Interfaculty Institute of Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bakula
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Takacs
authors.forename: Tassula
authors.initials: T
authors.lastname: Proikas-Cezanne
mesh_terms: D000595:Amino Acid Sequence; D001343:Autophagy; D006801:Humans; D008136:Longevity; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes; D010716:Phosphatidylinositols; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases