Membranes. The origin of the membranes composing autophagosomes is a long-standing mystery in the field of autophagy. A major difficulty in addressing this question has been that phagophores as well as autophagosomes do not contain marker proteins of other subcellular compartments [55, 56] . A series of new studies has implicated several cellular organelles as the possible source for the autophagosomal lipid bilayers. The plasma membrane and elements of the trafficking machinery to the cell surface have been linked to the formation of an early autophagosomal intermediate, perhaps the phagophore [57] [58] [59] [60] [61] . It is possible that early endosomal-and/or Golgiderived membranes are also key factors in the initial steps of autophagy [34, 36, 39] . The Golgi, moreover, appears also important for autophagy by supplying at least in part the extra lipids required for the phagophore expansion [29, [62] [63] [64] [65] . The endoplasmic reticulum (ER) is also central in this latter event. While the relevance of the ER in autophagosome biogenesis was already pointed out a long time ago [5, 55, 66, 67] , recently two electron tomography studies have demonstrated the existence of a physical connection between the ER and the forming autophagosomes [68, 69] . These analyses have revealed that the ER is connected to the outer as well as the inner membrane of the phagophore through points of contact, supporting the notion that lipids could be supplied via direct transfer at the sites of membrane contact. In line with this view, it has been found that Atg14L is associated to the ER and PI3P is generated on specific subdomains of this organelle from where autophagosomes emerge under autophagy-inducing conditions [25, 70] (Figure 1 ). It has also been proposed that the outer membrane of the mitochondria is the main source of the autophagosomal lipid bilayers, but while the experimental evidences appear to show that mitochondria are essential for the phagophore expansion, it remains unclear whether these organelles play a key role in the phagophore biogenesis [71] . The discrepancy between the conclusions of the various studies has not allowed yet drawing a model about the membrane dynamics during autophagosome biogenesis. The different results could be due to the different experimental conditions and model systems used by the various laboratories. Alternatively, the lipids forming the autophagosomes could have different sources depending on the cell and the conditions inducing autophagy [72, 73] . A third possibility is that the source of phagophore membrane could depend on the nature of the double-membrane vesicle cargo. Additional investigations are required to shed light on these issues.