%0 Journal Article
%T Autophagy: New Questions from Recent Answers
%A Fulvio Reggiori
%J ISRN Molecular Biology
%D 2012
%R 10.5402/2012/738718
%X Macroautophagy (hereafter autophagy) is currently one of the areas of medical life sciences attracting a great interest because of its pathological implications and therapy potentials. The discovery of the autophagy-related genes (ATGs) has been the key event in this research field because their study has led to the acquisition of new knowledge about the mechanism of this transport pathway. In addition, the investigation of these genes in numerous model systems has revealed the central role that autophagy plays in maintaining the cell homeostasis. This process carries out numerous physiological functions, some of which were unpredicted and thus surprising. Here, we will review some of the questions about the mechanism and function of autophagy that still remain unanswered, and new ones that have emerged from the recent discoveries. 1. Introduction The basic mechanism of autophagy is the sequestration of the structure that has to be degraded by large cytoplasmic double-membrane vesicles called autophagosomes. The current model is that autophagosomes are formed by expansion and sealing of a small cistern known as the phagophore or isolation membrane (Figure 1) [1¨C5]. Once complete, they fuse with the mammalian lysosomes or plant and yeast vacuoles to expose their cargo to the hydrolytic interior of these compartments for degradation. In mammalian cells, this event is preceded by the fusion with vesicles of the endocytic pathway and/or endosomes, to form amphisomes (Figure 1) [6]. The metabolites generated in the lysosomes/vacuoles are subsequently transported in the cytoplasm and used as either an energy source or building blocks for the synthesis of new macromolecules. The phagophore is generated at a specialized site known as the phagophore assembly site or preautophagosomal structure (PAS) [1¨C5]. At this location, the key actors of this pathway, the autophagy-related genes (ATGs), mediate the formation of the phagophore and its expansion into an autophagosome. Sixteen Atg proteins compose the conserved core Atg machinery that catalyses the formation of autophagosomes in all eukaryotes. The rest of the Atg proteins are organism-specific and most of them are involved in either the regulation of autophagy or dictating the specificity during selective types of autophagy. Autophagy has been considered for long time a nonselective process for bulk degradation of either long-lived proteins or cytoplasmic components during nutrient deprivation. Recent evidences, however, have revealed the existence of numerous types of selective autophagy used by the cell to
%U http://www.hindawi.com/journals/isrn.molecular.biology/2012/738718/