The IAP family member BRUCE regulates autophagosome–lysosome fusion

Petra Ebner, Isabella Poetsch, Luiza Deszcz, Thomas Hoffmann, Johannes Zuber and Fumiyo Ikeda ()
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Petra Ebner: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA)
Isabella Poetsch: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA)
Luiza Deszcz: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA)
Thomas Hoffmann: Research Institute of Molecular Pathology (IMP)
Johannes Zuber: Research Institute of Molecular Pathology (IMP)
Fumiyo Ikeda: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA)

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-02823-x

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