2007 Fiscal Year Final Research Report Summary
Regulation of autophagyby the endocrine systems
| Project/Area Number |
18370084
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MIZUSHIMA Noboru Tokyo Medical and Dental University, Physiology and Cell Biology, Professor (10353434)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Autopahgy / Insulin / Diabetes Mellitus / Amino acid / mTOR / FIP200 / ULK |
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| Research Abstract |
The purpose of this project is to understand how autophagy is regulated, particularly by the endocrine systems. We first analyzed the involvement of mTOR, a master regulator of nutrient sensing, to reveal the autophagy regulation under physiological conditions. We found that suppression of mTOR activity correlated very well with autophagy induction following food withdrawal in mice. This result suggested that mTOR plays an important role in autophagy regulation in whole animals. Next we analyzed the role of the insulin signaling, which is upstream of mTOR, by using diabetes model mice. In the STZ-induced type 1 diabetes model, autophagy was actively induced in various organs such as the heart, muscle and liver even under fed conditions, while autophagy was suppressed in normal mice. Autophagy induction in the STZ mice was partially suppressed by insulin administration. However autophagy was further activated even in these insulin-deficient mice. Taken together these data suggest that although insulin is the major inhibitory factor of autophagy in vivo, there must be other factors that could regulate autophagy induced by starvation In addition, we identified a novel ULK1-interacting autophagy factor FIP200, which functions downstream of mTOR FIP200 is required for autophagy induced by either amino acid-starvation or growth factor-starvation Further analyses of the relationship between mTOR and the FIP200/ULK complex will reveal the precise mechanism of autophagy regulation and induction.
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