WIPI β-propellers in autophagy-related diseases and longevity

Biochem Soc Trans. 2013 Aug;41(4):962-7. doi: 10.1042/BST20130039.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Autophagy*
  • Humans
  • Longevity*
  • Mechanistic Target of Rapamycin Complex 1
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Multiprotein Complexes / physiology
  • Phosphatidylinositols / metabolism
  • Protein Binding
  • Sequence Homology, Amino Acid
  • TOR Serine-Threonine Kinases / physiology

Substances

  • Membrane Proteins
  • Multiprotein Complexes
  • Phosphatidylinositols
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1