Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy

Yoshinori Takahashi, Cheryl L. Meyerkord, Tsukasa Hori, Kristin Runkle, Todd E. Fox, Mark Kester, Thomas P. Loughran, Hong Gang Wang

Research output: Contribution to journalArticle

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Abstract

Atg9 is a transmembrane protein essential for autophagy which cycles between the Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells during starvation through a mechanism that is dependent on ULK1 and requires the activity of the class III phosphatidylinositol-3-kinase (PI3KC3). In this study, we demonstrate that the N-BAR-containing protein, Bif-1, is required for Atg9 trafficking and the fission of Golgi membranes during the induction of autophagy. Upon starvation, Atg9-positive membranes undergo continuous tubulation and fragmentation to produce cytoplasmic punctate structures that are positive for Rab5, Atg16L and LC3. Loss of Bif-1 or inhibition of the PI3KC3 complex II suppresses starvation-induced fission of Golgi membranes and peripheral cytoplasmic redistribution of Atg9. Moreover, Bif-1 mutants, which lack the functional regions of the N-BAR domain that are responsible for membrane binding and/or bending activity, fail to restore the fission of Golgi membranes as well as the formation of Atg9 foci and autophagosomes in Bif-1-deficient cells starved of nutrients. Taken together, these findings suggest that Bif-1 acts as a critical regulator of Atg9 puncta formation presumably by mediating Golgi fission for autophagosome biogenesis during starvation.

Original languageEnglish (US)
Pages (from-to)61-73
Number of pages13
JournalAutophagy
Volume7
Issue number1
DOIs
StatePublished - Jan 2011

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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