Membrane ATG8ylation in secretory autophagy

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• Autophagy related (ATG) proteins are essential for lysosomal degradation.
• ATG proteins also mediate non-degradative processes, including unconventional protein secretion.
• Secretory autophagy relies on ATG8 proteins conjugated to membranes for cargo trafficking and extracellular release.

Purpose of the Study:

• To review the current understanding of how membrane ATG8ylation supports secretory autophagy.
• To propose a cell biological framework for classifying secretory autophagy pathways.
• To detail the emerging roles of secretory autophagy in physiology and disease.

Main Methods:

• Literature review of existing research on ATG8 proteins and secretory autophagy.
• Development of a classification framework based on membrane ATG8ylation sites.
• Analysis of reported physiological and pathological roles of secretory autophagy pathways.

Main Results:

• Membrane ATG8ylation is a key mechanism specifying and trafficking cargo for secretion.
• A framework is proposed to classify secretory autophagy pathways based on ATG8 conjugation at discrete vesicular intermediates.
• Emerging evidence highlights the involvement of these pathways in various physiological processes and diseases.

Conclusions:

• Membrane ATG8ylation is central to diverse forms of secretory autophagy.
• The proposed classification framework aids in understanding the heterogeneity of these pathways.
• Secretory autophagy pathways represent a significant area of investigation for understanding health and disease.