Hrr25 triggers selective autophagy-related pathways by phosphorylating receptor proteins

J Cell Biol. 2014 Oct 13;207(1):91-105. doi: 10.1083/jcb.201402128. Epub 2014 Oct 6.


In selective autophagy, degradation targets are specifically recognized, sequestered by the autophagosome, and transported into the lysosome or vacuole. Previous studies delineated the molecular basis by which the autophagy machinery recognizes those targets, but the regulation of this process is still poorly understood. In this paper, we find that the highly conserved multifunctional kinase Hrr25 regulates two distinct selective autophagy-related pathways in Saccharomyces cerevisiae. Hrr25 is responsible for the phosphorylation of two receptor proteins: Atg19, which recognizes the assembly of vacuolar enzymes in the cytoplasm-to-vacuole targeting pathway, and Atg36, which recognizes superfluous peroxisomes in pexophagy. Hrr25-mediated phosphorylation enhances the interactions of these receptors with the common adaptor Atg11, which recruits the core autophagy-related proteins that mediate the formation of the autophagosomal membrane. Thus, this study introduces regulation of selective autophagy as a new role of Hrr25 and, together with other recent studies, reveals that different selective autophagy-related pathways are regulated by a uniform mechanism: phosphoregulation of the receptor-adaptor interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / metabolism
  • Autophagy / physiology*
  • Autophagy-Related Proteins
  • Binding Sites / genetics
  • COP-Coated Vesicles / metabolism
  • Casein Kinase I / genetics
  • Casein Kinase I / metabolism*
  • GTPase-Activating Proteins / metabolism
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism
  • Mutation
  • Peroxins
  • Peroxisomes / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Transport
  • Receptors, Cell Surface / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Vesicular Transport Proteins / metabolism*


  • ATG19 protein, S cerevisiae
  • ATG36 protein, S cerevisiae
  • Atg11 protein, S cerevisiae
  • Autophagy-Related Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • PEX3 protein, S cerevisiae
  • Peroxins
  • Receptors, Cell Surface
  • SEC23 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Casein Kinase I
  • HRR25 protein, S cerevisiae
  • Aminopeptidases
  • APE1 protein, S cerevisiae