Essential and distinct roles of phosphatidylinositol 4-kinases, Pik1p and Stt4p, in yeast autophagy

Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Sep;1864(9):1214-1225. doi: 10.1016/j.bbalip.2019.05.004. Epub 2019 May 21.


Autophagy is a degradative cellular pathway that protects eukaryotic cells from starvation/stress. Phosphatidylinositol 4-kinases, Pik1p and Stt4p, are indispensable for autophagy in budding yeast, but participation of PtdIns-4 kinases and their product, phosphatidylinositol 4-phosphate [PtdIns(4)P], is not understood. Nanoscale membrane lipid distribution analysis showed PtdIns(4)P is more abundant in yeast autophagosomes in the luminal leaflet than the cytoplasmic leaflet. PtdIns(4)P is confined to the cytoplasmic leaflet of autophagosomal inner and outer membranes in mammalian cells. Using temperature-conditional single PIK1 or STT4 PtdIns 4-kinase mutants, autophagic bodies in the vacuole of PIK1 and STT4 mutant cells dramatically decreased at restrictive temperatures, and the number of autophagosomes in the cytosol of PIK1 mutants cells was also decreased, whereas autophagosome levels of STT4 mutant cells were comparable to that of wild-type and STT4 mutant cells at permissive temperatures. Localization of PtdIns(4)P in the luminal leaflet in the biological membrane is a novel finding, and differences in PtdIns(4)P distribution suggest substantial differences between yeast and mammals. We also demonstrate in this study that Pik1p and Stt4p play essential roles in autophagosome formation and autophagosome-vacuole fusion in yeast cells, respectively.

Keywords: Autophagosome; Electron microscopy; Freeze–fracture; Lipid; Nanometer scale; Vacuole fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / analysis
  • 1-Phosphatidylinositol 4-Kinase / metabolism*
  • Autophagosomes / metabolism
  • Autophagosomes / ultrastructure
  • Autophagy
  • Phosphatidylinositol Phosphates / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / analysis
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Vacuoles / metabolism
  • Vacuoles / ultrastructure


  • Phosphatidylinositol Phosphates
  • Saccharomyces cerevisiae Proteins
  • phosphatidylinositol 4-phosphate
  • 1-Phosphatidylinositol 4-Kinase
  • PIK1 protein, S cerevisiae
  • STT4 protein, S cerevisiae