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Vol. 15, Issue 3, 1101-1111, March 2004
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* Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan;
Time's Arrow and Biosignaling, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan;
Unit Process and Combined Circuit, PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan;
** CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan;
¶ Department of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan;
|| Department of Molecular Biomechanics, School of Life Science, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan; and
# Department of Cell Genetics, National Institute of Genetics, Mishima, Japan
Submitted September 28, 2003;
Revised December 3, 2003;
Accepted December 3, 2003
Monitoring Editor: Jean Gruenberg
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.
Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E03–09–0704. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E03-09-0704.
Corresponding author. E-mail address: nmizu{at}nibb.ac.jp.
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