Cells in multicellular organisms constantly experience diverse stresses, including protein misfolding, organelle damage, scarcity of nutrients/energy and invasion by pathogens. One mechanism exploited by cells to combat stresses is the lysosome-mediated degradation of intracellular components via autophagy. Autophagy involves the formation of an isolation membrane (or phagophore), which further expands and closes to form the double-membrane autophagosome 1-3 . The mechanism of autophagosome formation was excellently reviewed recently 3 . Various cellular materials can be sequestered in autophagosomes, including unselected cytosolic material or selected cargos such as protein aggregates, damaged organelles and pathogens. Following autophagosome closure via membrane abscission, cargos are delivered to the vacuole (yeasts and plants) or to lysosomes (animal cells) (for an overview of the autophagy process see [4][5][6][7][8] ; Box 1). After degradation of the autophagic cargo, the digested content in the autolysosomes is released and lysosomes are re-formed to sustain the autophagic flux (Box 2). A series of proteins encoded by ATG (autophagy-related) genes and EPG (ectopic PGL granules) genes -identified mainly from genetic screens in Saccharomyces cerevisiae and Caenorhabditis elegans, respectively -act at different membrane remodelling steps for autophagosome formation and maturation 3,4,9,10 .In yeast, autophagosomes are formed in the vicinity of and directly fuse with the much larger vacuole, whereas in multicellular organisms, newly formed autophagosomes fuse with different endolysosomal vesicles such as early/late endosomes and lysosomes to form non-degradative, single-membrane structures called 'amphisomes' , which gradually acquire