In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent Autophagosome Marker
- 1 March 2004
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 15 (3), 1101-1111
- https://doi.org/10.1091/mbc.e03-09-0704
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.Keywords
This publication has 56 references indexed in Scilit:
- Yeast autophagosomes: de novo formation of a membrane structureTrends in Cell Biology, 2002
- Human Apg3p/Aut1p Homologue Is an Authentic E2 Enzyme for Multiple Substrates, GATE-16, GABARAP, and MAP-LC3, and Facilitates the Conjugation of hApg12p to hApg5pPublished by Elsevier BV ,2002
- Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem CellsThe Journal of cell biology, 2001
- LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processingThe EMBO Journal, 2000
- A New Protein Conjugation System in HumanPublished by Elsevier BV ,1998
- Excessive degradation of intracellular protein in macrophages prevents presentation in the context of major histocompatibility complex class II moleculesEuropean Journal of Immunology, 1997
- Isolation and characterization of autophagy‐defective mutants of Saccharomyces cerevisiaeFEBS Letters, 1993
- Autophagy and other vacuolar protein degradation mechanismsCellular and Molecular Life Sciences, 1992
- Efficient selection for high-expression transfectants with a novel eukaryotic vectorGene, 1991
- Morphometrical and immunocytochemical studies on rat pancreatic acinar cells under control and experimental conditionsBiology of the Cell, 1985