The Origin of Autophagosomes: The Beginning of an End

Autophagy is a catabolic intracellular process highly conserved among eukaryotes. During this process cytoplasmic material and organelles are surrounded and enclosed by double-membranes, forming vesicles called autophagosomes. Fusion of the autophagosomes with the lysosome/vacuole permits to expose the inner membrane compartment to lytic enzymes allowing the degradation of the engulfed cellular components. Autophagy has been shown to be an essential process for the cell survival in a multitude of situations. At a basal level, this catabolic pathway allows the removal of protein aggregates and/or damaged organelles to preserve the cell homeostasis. Under diverse pathological and physiological situations, the cell responds by increasing the levels of autophagy activity to cope with developmental adaptations or stresses. As a result, autophagy onset is observed in numerous diseases including neurodegenerative disorders, cancer, and myopathies. The cellular roles of autophagy as well as the function of the autophagy related (Atg) proteins have been extensively studied in the last decade and significant advances have been achieved. However, a multitude of questions still have to be answered before understanding the regulation and mechanism of autophagy in its full complexity. One of the enigmas in the field of autophagy is the origin of the lipid bilayers composing autophagosomes. While a considerable effort has been invested in solving this question during the past years, a consensus has not been reached yet. In this chapter, we discuss the studies, large part performed in yeast and mammalian cells, which propose several organelles of the eukaryotic cell including the endoplasmic reticulum (ER), Golgi, mitochondria, endosomes, and plasma membrane, as the source of autophagosomal membranes