Starvation controls late autophagy steps

Cellular material that is destined for degradation is enclosed by a double-membraned vesicle during the process of autophagy. The resulting autophagosome matures and fuses with lysosomes to complete cargo degradation. Besides quality control, autophagy is a response pathway to stresses such as starvation, during which autophagosomes are formed. However, it is unknown whether the later stages of mammalian autophagosome maturation and lysosome fusion are regulated by starvation. In their Research Article (Kuchitsu et al., 2018), Naonobu Fujita, Mitsunori Fukuda and co-workers address this using a knockout cell line for the small GTPase Rab7, known to be required for autophagy in several model organisms. The authors demonstrate that absence of Rab7 causes accumulation of autolysosomes, but not autophagosomes, in fed conditions. Interestingly, a brief starvation of the cells led to clearance of these autolysosomes. This is dependent on the presence of glutamine and, in addition, autolysosome maturation is also observed in starved wild-type cells. Thus, Rab7 is dispensable for mammalian autophagosome–lysosome fusion, which is a process that is regulated by starvation. Furthermore, this process is independent of the central autophagy regulator mammalian target of rapamycin complex 1 (mTORC1). This study highlights a new concept of a general regulation of autolysosome maturation by nutrient starvation in mammals.