Evolutionary trends and functional anatomy of the human expanded autophagy network

This analysis confirms the eukaryotic origin of autophagy core genes while it points to a diverse evolutionary history of autophagy receptors. Next, we used module identification to describe the functional anatomy of the network at the level of pathway modules. In addition to obvious pathways (e.g., lysosomal degradation, insulin signaling) our data unveil the existence of context-related modules such as Rho GTPase signaling.

Last, we used a tripartite, image-based RNAi – screen to test candidate genes predicted to play a role in regulation of autophagy. We verified the Rho GTPase, CDC42 , as a novel regulator of autophagy-related signaling. This study emphasizes the applicability of system-wide approaches to gain novel insights into a complex biological process and to describe the human autophagy pathway at a hitherto unprecedented level of detail.