CONICET | Buscador de Institutos y Recursos Humanos

During the last decade, autophagy has been pointed out as a central process incellular homeostasis with the consequent implication in most cellular settings andhuman diseases pathology. At present, there is significant data available about molecularmechanisms that regulate autophagy. Nevertheless, autophagy pathway itself and itsimportance in different cellular aspects are still not completely clear. In this article,we are focused in four main aspects: (a) Induction of Autophagy: Autophagy is anevolutionarily conserved mechanism induced by nutrient starvation or lack of growthfactors. In higher eukaryotes, autophagy is a cell response to stress which startsas a consequence of organelle damage, such as oxidative species and other stressconditions. (b) Initiation of Autophagy; The two major actors in this signaling processare mTOR and AMPK. These multitasking protein complexes are capable to summarizethe whole environmental, nutritional, and energetic status of the cell and promote theautophagy induction by means of the ULK1-Complex, that is the first member in theautophagy initiation. (c) ULK1-Complex: This is a highly regulated complex responsiblefor the initiation of autophagosome formation. We review the post-transductionalmodifications of this complex, considering the targets of ULK1. (d)The mechanismsinvolved in autophagosome formation. In this section we discuss the main events thatlead to the initial structures in autophagy. The BECN1-Complex with PI3K activity andthe proper recognition of PI3P are one of these. Also, the transmembrane proteins,such as VMP1 and ATG9, are critically involved. The membrane origin and the cellularlocalization of autophagosome biogenesis will be also considered. Hence, in this articlewe present an overview of the current knowledge of the molecular mechanisms involvedin the initial steps of mammalian cell autophagosome biogenesis.