The IAP family member BRUCE regulates autophagosome-lysosome fusion

Petra Ebner, Isabella Poetsch, Luiza Deszcz, Thomas Hoffmann, Johannes Zuber, Fumiyo Ikeda

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Autophagy has an important role in cellular homeostasis by degrading and recycling cytotoxic components. Ubiquitination is known to target cargoes for autophagy; however, key components of this pathway remain elusive. Here we performed an RNAi screen to uncover ubiquitin modifiers that are required for starvation-induced macroautophagy in mammalian cells. Our screen uncovered BRUCE/Apollon/Birc6, an IAP protein, as a new autophagy regulator. Depletion of BRUCE leads to defective fusion of autophagosomes and lysosomes. Mechanistically, BRUCE selectively interacts with two ATG8 members GABARAP and GABARAPL1, as well as with Syntaxin 17, which are all critical regulators of autophagosome-lysosome fusion. In addition, BRUCE colocalizes with LAMP2. Interestingly, a non-catalytic N-terminal BRUCE fragment that is sufficient to bind GABARAP/GABARAPL1 and Syntaxin 17, and to colocalize with LAMP2, rescues autolysosome formation in Bruce -/- cells. Thus, BRUCE promotes autolysosome formation independently of its ubiquitin-conjugating activity and is a regulator of both macroautophagy and apoptosis.

Original languageEnglish
Number of pages1
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - Feb 9 2018
Externally publishedYes

Fingerprint

Qa-SNARE Proteins
lysosomes
regulators
Autophagy
Ubiquitin
Lysosomes
Fusion reactions
fusion
Recycling
homeostasis
cargo
Cells
apoptosis
Apoptosis
recycling
depletion
fragments
Ubiquitination
proteins
Starvation

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

The IAP family member BRUCE regulates autophagosome-lysosome fusion. / Ebner, Petra; Poetsch, Isabella; Deszcz, Luiza; Hoffmann, Thomas; Zuber, Johannes; Ikeda, Fumiyo.

In: Nature communications, Vol. 9, No. 1, 09.02.2018.

Research output: Contribution to journalArticle

Ebner, Petra ; Poetsch, Isabella ; Deszcz, Luiza ; Hoffmann, Thomas ; Zuber, Johannes ; Ikeda, Fumiyo. / The IAP family member BRUCE regulates autophagosome-lysosome fusion. In: Nature communications. 2018 ; Vol. 9, No. 1.
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