Bidirectional interplay between peroxisomal hydrogen peroxide emission and autophagy
Peroxisomes are remarkably dynamic cell organelles that are best known for their role in cellular lipid and hydrogen peroxide metabolism. Over the years, it has become increasingly clear that redundant or dysfunctional peroxisomes are mainly degraded by the autophagy-lysosome pathway, in a process known as pexophagy. In addition, emerging evidence supports the concept that defects in this poorly-understood process are linked to multiple genetic (e.g., Zellweger syndrome) and oxidative stress-related (e.g., neurodegeneration, diabetes, and cancer) diseases, which pose a substantial burden on patients, their families, and society. This research project is intended to improve our understanding of the molecular mechanisms and signalling pathways that underlie the reciprocal interplay between peroxisome functioning and (selective) autophagy in mammalian cells, with a focus on the involvement of oxidative stress. On one hand, the project will focus on how peroxisomal hydrogen peroxide emission participates in general and selective autophagy regulation. On the other hand, it aims to dissect how perturbations in autophagy exacerbate or mitigate injury caused by peroxisome dysfunction, with a focus on redox balance. As such, the outcomes of this basic knowledge-driven project are an important first step toward the development of new strategies aimed at improving the outcomes of patients suffering from the above listed diseases.