In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent Autophagosome Marker

• Noboru Mizushima

  Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan

• Akitsugu Yamamoto

  Department of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan

• Makoto Matsui

  Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan

• Tamotsu Yoshimori

  CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan

• Yoshinori Ohsumi

  Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan

Abstract

Macroautophagy mediates the bulk degradation of cytoplasmic components. It accounts for the degradation of most long-lived proteins: cytoplasmic constituents, including organelles, are sequestered into autophagosomes, which subsequently fuse with lysosomes, where degradation occurs. Although the possible involvement of autophagy in homeostasis, development, cell death, and pathogenesis has been repeatedly pointed out, systematic in vivo analysis has not been performed in mammals, mainly because of a limitation of monitoring methods. To understand where and when autophagy occurs in vivo, we have generated transgenic mice systemically expressing GFP fused to LC3, which is a mammalian homologue of yeast Atg8 (Aut7/Apg8) and serves as a marker protein for autophagosomes. Fluorescence microscopic analyses revealed that autophagy is differently induced by nutrient starvation in most tissues. In some tissues, autophagy even occurs actively without starvation treatments. Our results suggest that the regulation of autophagy is organ dependent and the role of autophagy is not restricted to the starvation response. This transgenic mouse model is a useful tool to study mammalian autophagy.

Journal

• Molecular Biology of the Cell

  Molecular Biology of the Cell 15 (3), 1101-1111, 2004-03

  American Society for Cell Biology (ASCB)

Keywords

• Cell Biology
• Molecular Biology

Details

• CRID: 1360574094986697856
• NII Article ID: 30018378960
• DOI: 10.1091/mbc.e03-09-0704
• ISSN: 19394586
• ISSN: 10591524
• ISSN: http://id.crossref.org/issn/10591524
• Data Source:
  • Crossref
  • CiNii Articles