| Budget Amount *help |
¥488,800,000 (Direct Cost: ¥376,000,000、Indirect Cost: ¥112,800,000)
Fiscal Year 2007: ¥80,600,000 (Direct Cost: ¥62,000,000、Indirect Cost: ¥18,600,000)
Fiscal Year 2006: ¥98,800,000 (Direct Cost: ¥76,000,000、Indirect Cost: ¥22,800,000)
Fiscal Year 2005: ¥104,000,000 (Direct Cost: ¥80,000,000、Indirect Cost: ¥24,000,000)
Fiscal Year 2004: ¥106,600,000 (Direct Cost: ¥82,000,000、Indirect Cost: ¥24,600,000)
Fiscal Year 2003: ¥98,800,000 (Direct Cost: ¥76,000,000、Indirect Cost: ¥22,800,000)
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| Research Abstract |
Recently autophagy is getting a hot field in cell biology. There appeared many papers showing physiological significance of autophagy in many important aspects in mammals. However, molecular mechanism of autophagy is still remained to be uncovered. This research project aimed to understand the dynamics of membrane during autophgy at molecular level. For 4 years of the research period, we could obtain the following progress.
Total 18 Atg proteins are essential for autophagosome formation and consist five functional units. We systematically studied localization of each Atg proteins in every atg mutant and proposed hierarchy of Atg proteins for autophagosome formation. Furthermore auophagy-specific Atg protein complex (Atg17-Atg29-Atg31) was found to be basal for PAS formation for autophagosome.
Two conjugation systems are essential for autophagy. In vitro reconstitution of Atg12 conjugation and Atg8 lipidation was established using purified yeast and plant proteins. We succeeded to show Atg8-PE causes membrane tethering and hemifusion of PE-containing liposome. Also we showed that Atg12-Atg5 conjugate catalytically stimulate the Atg8 lipidation reaction like E3 enzyme.
Localization of autophagy-specific PI3-kinase was determined by Atg14 and PI3 kinase activity and its product PI3P are required for autophagosome formation.
In collaboration with Dr. Inagaki's group we succeeded to obtain crystal structures of LC3, Atg3, Atg4B, Atg4b-LC3 complex, Atg5/Atg16 complex, and Ape1.
It was shown that autophagy is essential for maintenance of amino acid levels for protein synthesis during nitrogen starvation.
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