Lysosomal microautophagy: an emerging dimension in mammalian autophagy.

Recent studies have unveiled the role of lysosomal (or vacuolar) microautophagy in organelle turnover and proteostasis from yeast to mammals. The recognition of (K63-)ubiquitinated proteins by the ESCRT complex is required for lysosomal (or vacuolar) microautophagic degradation for some proteins. The defect of lysosomal microautophagy of innate immune protein STING is suggested to be linked to neurodegenerative diseases. Understanding of the mechanism that underlies the cooperation of macroautophagy and microautophagy will be essential to decipher their distinct and general roles in cellular catabolic processes. Autophagy is a self-catabolic process through which cellular components are delivered to lysosomes for degradation. There are three types of autophagy, i.e., macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy. In macroautophagy, a portion of the cytoplasm is wrapped by the autophagosome, which then fuses with lysosomes and delivers the engulfed cytoplasm for degradation. In CMA, the translocation of cytosolic substrates to the lysosomal lumen is directly across the limiting membrane of lysosomes. In microautophagy, lytic organelles, including endosomes or lysosomes, take up a portion of the cytoplasm directly. Although macroautophagy has been investigated extensively, microautophagy has received much less attention. Nonetheless, it has become evident that microautophagy plays a variety of cellular roles from yeast to mammals. Here we review the very recent updates of microautophagy. In particular, we focus on the feature of the degradative substrates and the molecular machinery that mediates microautophagy. [ABSTRACT FROM AUTHOR]