Autophagy is the highly conserved process of degradation of cellular components in eukaryotes with the aim of maintaining cell homeostasis. The contribution to protein degradation by autophagy is similar in magnitude to that of the ubiquitin-proteasome system. Defects in the autophagy process can lead to various (e.g., neurodegenerative) diseases. Autophagy requires a whole series of so-called autophagy-related (Atg) proteins, and in higher organisms entire protein families have evolved from an ancestral Atg protein in many cases.

One such example is the Atg8 protein family, an interesting family of small ubiquitin-like modifiers. In humans, there two Atg8 subfamilies, known as LC3s and GABARAPs. These proteins fulfill diverse tasks in the macroautophagy pathway, e.g. during its initiation, expansion and the transport of autophagosomes, but also as cargo receptors. The more general concept of “atg8ylation” emphasizes - analogous to ubiquitination - the property of Atg8-like proteins to make stressed or remodeled membrane systems “visible” to the cell due to being conjugated to lipids.

Our goal is to identify previously neglected functions of GABARAP-like proteins in fundamental cellular processes beyond autophagy, including Golgi maintenance, protein trafficking, vesicle transport, and unconventional protein secretion. Some of these are potentially of relevance for clearing amyloid protein aggregates, which can trigger neurodegeneration. One of our aims is to utilize selected human Atg8 proteins as part of targeted protein degradation strategies, particularly for amyloid clearance.