AMBRA1-regulated autophagy in vertebrate development
Published: 2 September 2015
Manuela Antonioli1,2, Federica Albiero1, Gian María Fimia1,3 and Mauro Piacentini*,1,2
1National Institute for Infectious Diseases I.R.C.C.S. ‘Lazzaro Spallanzani’ Rome, 2Department of Biology, University of Rome ‘Tor Vergata’, Rome, and 3Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy
Autophagy is a catabolic process that mediates the lysosomal turn over of organelles and macromolecules, and is strongly activated in stress conditions to ensure cell survival. Autophagy core genes are highly conserved from yeast to mammals, with an increasing number of positive and negative regulators that have evolved in higher eukaryotes. Autophagy takes part in different stages of development, as revealed by alterations in cell proliferation, differentiation and survival during the embryogenesis of organisms carrying mutations in autophagy genes. These defects are ascribed to the ability of autophagy to provide elements for new synthesis or energy production in limiting conditions during embryogenesis, as well as to contribute to the profound cell remodeling that occurs during differentiation. However, many differences have been observed in the phenotypes of autophagy mutant organisms, indicating that these genes have acquired specific functions in particular tissues, which may reflect the ability of autophagy to crosstalk with the main developmental processes. In this review, we discuss the role of upstream regulators of autophagy in the development of different model systems, focusing, in particular, on AMBRA1 (autophagy/beclin-1 regulator-1) and its role in the central nervous system.