The role of autophagy in mammalian development: cell makeover rather than cell death.
Autophagy is important for the degradation of bulk cytoplasm, long-lived proteins, and entire organelles. In lower eukaryotes, autophagy functions as a cell death mechanism or as a stress response during development. However, autophagy's significance in vertebrate development, and the role (if any) of vertebrate-specific factors in its regulation, remains unexplained. Through careful analysis of the current autophagy gene mutant mouse models, we propose that in mammals, autophagy may be involved in specific cytosolic rearrangements needed for proliferation, death, and differentiation during embryogenesis and postnatal development. Thus, autophagy is a process of cytosolic "renovation," crucial in cell fate decisions.
Cecconi
Francesco
F
Dulbecco Telethon Institute at the Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy; Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy. Electronic address: francesco.cecconi@uniroma2.it.
Levine
Beth
B
Howard Hughes Medical Institute, Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA; Department of Internal Medicine, Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA; Department of Microbiology, Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA. Electronic address: beth.levine@utsouthwestern.edu.
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D016923:Cell Death / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D010588:Phagosomes / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C521754:Ambra1 protein, mouse; D051017:Apoptosis Regulatory Proteins; C495773:Atg5 protein, mouse; C502661:Atg7 protein, mouse; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D000071193:Autophagy-Related Protein 7