Functions of Autophagy Proteins in Lysosome-Dependent and -Independent Mechanisms

Autophagy is a fundamental biological process that impacts nearly all facets of human health and plays critical roles in many human diseases, especially inflammatory and neurodegenerative diseases, as well as cancer. During the autophagy process, cellular components are sequestered into double-membrane vesicles targeted for lysosomal degradation by a set of evolutionary conserved autophagy-related genes, which in turn ensure homeostasis at the cellular, tissue and organismal level. Aside from intense research on autophagy's broad physiological roles, the autophagy field is currently challenged with understanding the detailed molecular underpinnings of autophagy, including the basis for how different cellular components are selectively targeted for lysosomal degradation. Interestingly, the molecular studies of the autophagy process have pointed towards a new and emerging concept in the field, namely that many autophagy-related proteins have functions outside of lysosomal degradation, for example in other membrane-trafficking and signaling pathways. Our current understanding of the physiological roles of autophagy are largely derived from studies of cells and organisms deficient in single autophagy genes; considering the emerging concept that many autophagy proteins could have functions outside lysosomal degradation, the field may need to re-evaluate the physiological functions of autophagy.

The 2022 Autophagy GRC will be instrumental in communicating the newest molecular insights of the biological functions of autophagy genes in lysosomal degradation and beyond, with the goal of facilitating translation of the presently acquired knowledge into drugs and novel treatments for autophagy-related diseases.