Graduate School of Frontier Biosciences, Osaka University

Japanese

Autophagosomes form at ER-mitochondria contact sites

Journal Nature (2013) in press
Authors Maho Hamasaki (1, 2, †), Nobumichi Furuta (3, †), Atsushi Matsuda (4, 5), Akiko Nezu (1, 2), Akitsugu Yamamoto (6), Naonobu Fujita (1, 2), Hiroko Oomori (7), Takeshi Noda (1, 2), Tokuko Haraguchi (4), Yasushi Hiraoka (5), Atsuo Amano (3, 8, *), Tamotsu Yoshimori (1, 2, *)
  1. Department of Genetics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
  2. Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  3. Department of Oral Frontier Biology, Center for Oral Frontier Science, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan
  4. National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe 651-2492, Japan
  5. Biomolecular Networks Laboratories Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
  6. Department of Cell Biology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan
  7. Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
  8. Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan

*To whom correspondence should be addressed:
E-mail: tamyoshi@fbs.osaka-u.ac.jp and amanoa@dent.osaka-u.ac.jp
Title Autophagosomes form at ER-mitochondria contact sites
Laboratory Laboratory of Intracellular Membrane Dynamics 〈Prof. Yoshimori〉
Abstract Autophagy is a tightly regulated intracellular bulk degradation/recycling system that has fundamental roles in cellular homeostasis. Autophagy is initiated by isolation membranes, which form and elongate as they engulf portions of the cytoplasm and organelles. Eventually isolation membranes close to form double membrane-bound autophagosomes and fuse with lysosomes to degrade their contents. The physiological role of autophagy has been determined since its discovery, but the origin of autophagosomal membranes has remained unclear. At present, there is much controversy about the organelle from which the membranes originate—the endoplasmic reticulum (ER), mitochondria and plasma membrane. Here we show that autophagosomes form at the ER–mitochondria contact site in mammalian cells. Imaging data reveal that the pre-autophagosome/autophagosome marker ATG14 (also known as ATG14L) relocalizes to the ER–mitochondria contact site after starvation, and the autophagosome-formation marker ATG5 also localizes at the site until formation is complete. Subcellular fractionation showed that ATG14 co-fractionates in the mitochondria-associated ER membrane fraction under starvation conditions. Disruption of the ER–mitochondria contact site prevents the formation of ATG14 puncta. The ER-resident SNARE protein syntaxin 17 (STX17) binds ATG14 and recruits it to the ER–mitochondria contact site. These results provide new insight into organelle biogenesis by demonstrating that the ER–mitochondria contact site is important in autophagosome formation.