Uba1 functions in Atg7- and Atg3-independent autophagy

Nat Cell Biol. 2013 Sep;15(9):1067-78. doi: 10.1038/ncb2804. Epub 2013 Jul 21.

Abstract

Autophagy is a conserved process that delivers components of the cytoplasm to lysosomes for degradation. The E1 and E2 enzymes encoded by Atg7 and Atg3 are thought to be essential for autophagy involving the ubiquitin-like protein Atg8. Here, we describe an Atg7- and Atg3-independent autophagy pathway that facilitates programmed reduction of cell size during intestine cell death. Although multiple components of the core autophagy pathways, including Atg8, are required for autophagy and cells to shrink in the midgut of the intestine, loss of either Atg7 or Atg3 function does not influence these cellular processes. Rather, Uba1, the E1 enzyme used in ubiquitylation, is required for autophagy and reduction of cell size. Our data reveal that distinct autophagy programs are used by different cells within an animal, and disclose an unappreciated role for ubiquitin activation in autophagy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Autophagy-Related Protein 7
  • Cell Size
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics
  • Epithelial Cells / cytology
  • Epithelial Cells / enzymology*
  • Gene Expression Regulation
  • Intestines / cytology
  • Intestines / enzymology*
  • Larva / cytology
  • Larva / enzymology*
  • Larva / genetics
  • Organ Specificity
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Signal Transduction
  • Ubiquitin / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Activating Enzymes / genetics
  • Ubiquitin-Activating Enzymes / metabolism*
  • Ubiquitin-Conjugating Enzymes / deficiency
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitination

Substances

  • Atg7 protein, Drosophila
  • Atg8a protein, Drosophila
  • Drosophila Proteins
  • Protein Isoforms
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Autophagy-Related Protein 7
  • Uba1 protein, Drosophila
  • Ubiquitin-Activating Enzymes