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The origin of the autophagosomal membrane


Macroautophagy is initiated by the formation of the phagophore (also called the isolation membrane). This membrane can both selectively and non-selectively engulf cytosolic components, grow and close around the sequestered components and then deliver them to a degradative organelle, the lysosome. Where this membrane comes from and how it grows is not well understood. Since the discovery of autophagy in the 1950s the source of the membrane has been investigated, debated and re-investigated, with the consensus view oscillating between a de novo assembly mechanism or formation from the membranes of the endoplasmic reticulum (ER) or the Golgi. In recent months, new information has emerged that both the ER and mitochondria may provide a membrane source, enlightening some older findings and revealing how complex the initiation of autophagy may be in mammalian cells.

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Figure 1: Potential sources for the phagophore include the Golgi complex, endosomes, ER and mitochondria.
Figure 2: Model for recruitment of Atg proteins and DFCP1 to the ER-derived membrane and formation of the phagophore.


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S.A.T. would like to thank Cancer Research U.K. for funding. T. Y. was supported by Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by the Takeda Science Foundation.

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Tooze, S., Yoshimori, T. The origin of the autophagosomal membrane. Nat Cell Biol 12, 831–835 (2010).

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