Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity

Yasuhiro Araki, Wei-Chi Ku, Manami Akioka, Alexander May, Yu Hayashi, Fumio Arisaka, Yasushi Ishihama, Yoshinori Ohsumi

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91 Citations (Scopus)


Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Delta cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15-Vps34 and Atg14-Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15-Vps34 and Atg14-Vps30 subcomplexes to facilitate complex I formation.
Original languageEnglish
Pages (from-to)299 - 313
Number of pages15
JournalJournal of Cell Biology
Issue number2
Publication statusPublished - 2013

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