Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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Outline of Final Research Achievements |
Upon induction of autophagy, a double membrane-bound autophagosome is generated and fuses with lysosomes to degrade its contents. However, it remains unclear how the ULK1 complex receives the autophagy-inducing signals from the mTORC1 complex. In this study, we found that the intrinsically disordered region (IDR) of ULK1 directly interacts with the mTORC1 complex. In yeast, the TORC1-interacting region is the IDR of Atg13. Thus, our findings indicate that the signal recognition system is shifted from Atg13 to ULK1 during evolution. We also identified the regions of ULK1, ATG13, and FIP200 involved in the formation of the ULK1 complex and found that the ULK1 complex further assembles with each other to form liquid droplet-like structures in vivo. We also found that ATG9 vesicles are recruited via selective autophagy substrates in addition to the ATG13-dependent pathway found in yeast. We show that mammals have acquired a selective autophagy substrate-dependent pathway during evolution.
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