Abstract:
Autophagy is an intracellular degradation system that involves biogenesis of a double membrane organelle named autophagosome. Autophagosome formation requires 18 core Atg proteins that constitute six functional groups, among which the Atg1 complex and the Atg8 and Atg12 ubiquitin-like conjugation systems function as the most upstream and downstream factors, respectively. In order to elucidate the molecular mechanisms of autophagy, we have been studying the structure and function of these Atg proteins. From the structural studies on the Atg1 complex, the molecular mechanisms of autophagy initiation upon starvation and its difference between yeast and mammals have been elucidated [1,2]. Furthermore, from the structural studies on the Atg8 and Atg12 conjugation systems, not only the mechanisms of unique conjugation reactions but also the molecular roles of these conjugation systems in the later steps of autophagy have begun to be uncovered. I would like to summarize these results and discuss the unsolved problems in autophagy machineries.

References:
[1] Structural basis of starvation-induced assembly of the autophagy initiation complex. Fujioka, Y., Suzuki, S. W., Yamamoto, H., Kondo-Kakuta, C., Kimura, Y., Hirano, H., Akada, R., Inagaki, F., *Ohsumi, Y. and *Noda, N. N. Nat. Struct. Mol. Biol. 21, 513-521 (2014).
[2] Structure of the Atg101-Atg13 complex reveals essential roles of Atg101 in mammalian autophagy initiation. Suzuki, H., Kaizuka, T., *Mizushima, N. and *Noda, N. N. Nat. Struct. Mol. Biol. 22, 572-580 (2015).
[3] Structural basis of Atg8 activation by a homodimeric E1, Atg7. *Noda, N. N., Satoo, K., Fujioka, Y., Kumeta, H., Ogura, K., Nakatogawa, H., Ohsumi, Y. and *Inagaki, F. Mol. Cell 44, 462-75 (2011).
[4] Non-canonical recognition and Ubl-loading of distinct E2s by autophagy-essential Atg7. Yamaguchi, M., Matoba, K., Sawada, R., Fujioka, Y., Nakatogawa, H., Yamamoto, H., Kobashigawa, Y., Hoshida, H., Akada, R., Ohsumi, Y., *Noda, N. N. and *Inagaki, F. Nat. Struct. Mol. Biol. 19, 1250-6 (2012).
[5] Structural basis of the differential function of the two C. elegans Atg8 homologs, LGG-1 and LGG-2, in autophagy. Wu, F., Watanabe, Y., Guo, X. Y., Qi, X., Wang, P., Zhao, H. Y., Wang, Z., Fujioka, Y., Zhang, H., Ren, J. Q., Fang, T. C., Shen, Y. X., Feng, W., Hu, J. J., *Noda, N. N. and *Zhang, H. Mol. Cell 60, 914-929 (2015).