The exact how and from where the autophagosome emerges is unspecified but a research has identified a site called pre-autophagosomal structure (PAS). Autophagy-related (ATG) proteins are the main substance involved in the PAS leading to autophagosomal production. The discovery of ATG proteins in the 1990s greatly advanced the understanding of autophagy and clarified that autophagy serves important roles in various biological processes. (Shibutani ST1,2, ). Phagophore, autophagosome and autophagolysosome formation are regulated by at least 30 ATG proteins. (I. M. Aparicio).
In recent years, the analysis of knockout models of ATG genes in mice revealed new knowledge about the functions of autophagy in mammalian cell development and differentiation. Embryos were divided into groups with various ATG genes deleted e.g. ATG5, ATG7, ATG3, etc…and and it was shown that deletion of some ATG genes leads to lethality mid-embryonic development, and the mice that survive postnatal period display some developmental abnormalities including an atypical lymphocyte differentiation. (Mizushima).