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Open sesame!
The autophagosome is a double-membraned intracellular structure involved in the disposal of damaged or defunct organelles. Autophagosome formation requires a number of autophagy-related (ATG) proteins. Among them, the key conjugation systems ATG8 and ATG12 are widely exploited in the detection of autophagy in many organisms. However, their precise function in autophagy remains unknown. Tsuboyama et al. identified an unexpected role of ATG3, an important enzyme in the ATG conjugation systems, in efficient degradation and opening of the inner autophagosomal membrane after fusion with lysosomes (see the Perspective by Levine). Their live-imaging system revealed the entire life of an autophagosome in mammalian cells.
Abstract
In macroautophagy, cytoplasmic contents are sequestered into the double-membrane autophagosome, which fuses with the lysosome to become the autolysosome. It has been thought that the autophagy-related (ATG) conjugation systems are required for autophagosome formation. Here, we found that autophagosomal soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) syntaxin 17–positive autophagosome-like structures could be generated even in the absence of the ATG conjugation systems, although at a reduced rate. These syntaxin 17–positive structures could further fuse with lysosomes, but degradation of the inner autophagosomal membrane was significantly delayed. Accordingly, autophagic activity in ATG conjugation–deficient cells was strongly suppressed. We suggest that the ATG conjugation systems, which are likely required for the closure (i.e., fission) of the autophagosomal edge, are not absolutely essential for autolysosome formation but are important for efficient degradation of the inner autophagosomal membrane.
