Angelina Gross: Autophagy regulation through stress-dependent plasticity of the autophagy initiationcomplex

Speaker: Angelina Gross / Institute of Molecular Plant Biology, BOKU University, Vienna, Austria

Abstract:

Autophagy regulation through stress-dependent plasticity of the autophagy initiation complex

Cells must rapidly convert complex stress signals into adaptive homeostatic responses. Autophagy, a highly conserved process, regulates the targeted degradation of cellular components to facilitate cellular reprograming in response to stress. Canonically, stress signals are integrated at the level of protein kinase networks acting upstream of the conserved Atg1/ULK kinase complex (AKC), which initiates both non-selective and selective forms of autophagy. Exploring autophagy initiation under phosphate starvation, we uncovered a mechanism of direct AKC regulation through the recruitment of the phosphate metabolite sensor Pho81 in yeast Saccharomyces cerevisiae [1]. We show that Pho81 directly interacts with the selective autophagy adaptor subunit Atg11/FIP200 at the AKC. While TORC1 remains largely active during phosphate starvation, Pho81 bypasses the TORC1-Atg13 axis and promotes Atg11-phosphorylation to drive pexophagy (the targeted degradation of peroxisomes). Thus, our work demonstrates, that Atg11/FIP200 not only binds selective autophagy receptors, but also modulator subunits regulating autophagy by conveying metabolic information to the AKC directly [1]. Currently, we expand upon these findings using the plant model Arabidopsis thaliana [2]. With our recently founded lab at BOKU University in Vienna, we investigate whether molecular plasticity within the AKC, including the recruitment of stress-adapted modulator subunits, is a conserved mechanism regulating plant autophagy initiation in response to a broad range of environmental stimuli. 

[1] Gross, A.S. et al. (2024). A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy. Nature Cell Biology. https://doi.org/10.1038/s41556-024-01348-4.

[2] Gross, A.S. et al. (2025). Autophagy in Plant Health and Disease. https://doi.org/10.1146/annurev-arplant-060324-094912. https://doi.org/10.1146/annurev-arplant-060324-094912.