TY - JOUR
T1 - Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy
AU - Takahashi, Yoshinori
AU - Meyerkord, Cheryl L.
AU - Hori, Tsukasa
AU - Runkle, Kristin
AU - Fox, Todd E.
AU - Kester, Mark
AU - Loughran, Thomas P.
AU - Wang, Hong Gang
N1 - Funding Information:
We thank N. Nakamura for technical advice on immunofluorescent analyses and K. El-Bayoumy for critical reading of the manuscript. This work is supported by grants from the James & Esther King Biomedical Research Program (08KN-15-17228) to Y.T., National Institutes of Health (CA82197 and CA129682), American Cancer Society (RSG-05-244-01-CCG) and Flight Attendant Medical Research Institute (FAMRI062463-CIA) to H.G.W.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
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U2 - 10.4161/auto.7.1.14015
DO - 10.4161/auto.7.1.14015
M3 - Article
C2 - 21068542
AN - SCOPUS:78650816366
SN - 1554-8627
VL - 7
SP - 61
EP - 73
JO - Autophagy
JF - Autophagy
IS - 1
ER -