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. 2018 Nov 19;7(11):215. doi: 10.3390/cells7110215

Figure 4.

Figure 4

Possible models of Rab7-dependent and -independent autolysosome maturation in mammalian cells. (A) Rab7 regulates the amphisome-lysosome fusion step. It has been suggested that during the process of autophagy, the autophagosome sequentially fuses with an endosome and with a lysosome to form an amphisome and an autolysosome, respectively. Loss of Rab7 would cause autolysosome accumulation, and glutamine starvation would rapidly induce lysosome fusion to the amphisome. (B) Rab7 regulates the efficiency of autophagosome-lysosome fusion. In this model, an autophagosome in a mammalian cell fuses with multiple lysosomes thereby enabling complete degradation of its content. Loss of Rab7 should result in a decrease in the number of lysosomes fused to the autophagosome and lead to autolysosome accumulation. Glutamine starvation may rapidly induce fusion of additional lysosomes to the autophagosome and result in complete degradation. (C) Rab7 regulates lysosomal functions by transporting lysosomal enzymes and/or lysosomal membrane proteins from the late endosome to the lysosome. Because delivery of lysosomal enzymes to lysosomes is partially impaired in Rab7-KO cells [17,25,26], this process may be upregulated by glutamine starvation. (D) Two independent SNARE complexes, the syntaxin17 (STX17)-SNAP29-VAMP8 complex and the syntaxin7 (STX7)-SNAP29-YKT6 complex, control autophagosome-lysosome fusion [29], consistent with the model shown in (B). Rab7 cooperates with the STX17-SNAP29-VAMP8 complex together with Rab2 and the HOPS complex in mediating autophagosome-lysosome fusion [13]. By contrast, the STX7-SNAP29-YKT6 complex is likely to be Rab7-independent and partially mediates the fusion even in the absence of Rab7. Future investigation will be necessary to determine whether glutamine starvation activates the function of the STX7-SNAP29-YKT6 complex. In contrast to this model, however, it has recently been proposed that two SNARE complexes, STX17-SNAP29-YKT6 and STX17-SNAP29-VAMP7/8, in fruit flies sequentially regulate autophagosome-lysosome fusion by replacing YKT6 with VAMP7/8 [30].