| Research Abstract |
To degrade their own components, cells possess autophagy that. delivers part of the cytosol and organelles into lysosomes. Autophagy contributes not only turnover of cellular constituents but also reconstruction of cells and tissue; it is induced circumstantially and degrades the intracellular structure at large-scale. Since abnormal induction of autophagy has been often observed in diverse diseases, pathological role of autophagy has the attention of investigators. In this project, we aimed for elucidation of molecular machinery of autophagy and its role in development, differentiation, and diseases.
Our results are as follows. 1) we identified mammalian Atg10 as a enzyme catalyzing covalent binding of Atg12 with Atg5, 2) we showed that fusion between autophagosomes and lysosomes requires transport from endosomes to autophagosomes, 3) we found a large 800kDa proteins complex including the Atg5-Atgl2 conjugate and identified a novel protein Atg16L as a component of the complex, 4) we obtained a evidence that lipidation of LC3 cause its localization to autophagosomes and demonstrated that two LC3 homologues, GABARAP and GATE16, could bind to autophagosomes like LC3, 5) we produced transgenic mouse expressing GFP-LC3 ubiquitously, which is useful to examine induction of autophagy during development and tissue differentiation,6) we found new function of autophagy ; autophagy prevents intracellular multiplication of both unfolded proteins causing degenerative diseases and pathogenic bacteria that have invaded host cells, 7) we discovered that mouse hepatitis virus related to coronavirus causing SARS utilizes autophagosomes to multiply inside host cells.
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