Microautophagy: The Least Known of the Autophagy Strategies

Dear Colleagues,

Canonical “Autophagy” refers to an evolutionarily conserved process through which cellular contents, such as damaged organelles and protein aggregates, are delivered to lysosomes for degradation. Autophagy is a highly conserved eukaryotic cellular recycling process. Different types of autophagy have been classified based on how they deliver cargo to lysosomes. At present, the prevailing categories of autophagy in mammalian cells are macroautophagy, microautophagy and chaperone-mediated autophagy. The molecular mechanisms and biological functions of macroautophagy and chaperone-mediated autophagy have been extensively studied, but microautophagy has received much less attention.

Microautophagy typically refers to the process by which cytosolic components are directly delivered to the surface of lysosomes. Cytoplasmic contents enter the lysosome via the invagination or deformation of the lysosomal membrane. With its constitutive characteristics, the microautophagy of soluble substrates can be induced by N-starvation or rapamycin via regulatory signalling complexes. This degradation system has been studied by examining two distinct pathways, i.e., the process of lysosomal membrane invagination facilitated by the endosomal sorting complex required for transport (ESCRT) complex and the formation of new lysosomal membrane protrusions mediated by autophagy-related proteins (ATG) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Microautophagy plays a critical role in maintaining organelle size, ensuring membrane stability, and promoting cell survival under conditions of nitrogen limitation. In mammalian cells, the precise regulatory mechanisms that control microautophagy are not fully understood. In contrast to the two other types of autophagy, i.e., macrophagy and chaperone-mediated autophagy, establishing representative models to study microautophagy is very challenging. As such, less is known about this system. Furthermore, understanding the mechanism that underlies the cooperation between macroautophagy and microautophagy will be essential to decipher their distinct and general roles in cellular catabolic processes.

The aim of this Special Issue is to provide an overview of the main signalling pathways and molecules involved in the process of microautophagy, highlighting their connection with macroautophagy and the generated interest regarding the more recent discovery of their therapeutic use.

Dr. Patrice X. Petit
Guest Editor

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• core autophagy machinery
• ESCRT machinery
• lysosomophagy
• membrane fission
• membrane fusion
• microautophagy
• SNAREs