Protein ubiquitination, as its name implies, is ubiquitous, and is emerging as a key regulator of protein homeostasis and cell signalling. Deregulation of protein ubiquitination is involved in a variety of human diseases, including cancer, neurodegenerative and inflammatory conditions. The last decade has shown that a plethora of distinct ubiquitin signals exist. My lab tries to understand the complex ‘ubiquitin code’ by focussing on the different ubiquitin signals themselves, in order to eventually link the specificity in the system back to physiological functions.
A major playground for ubiquitin research in the past five years has focussed on mitochondrial ubiquitination events that lead to mitophagy. This process involves the ubiquitin(-fold) kinase PINK1 and the E3 ligase Parkin. Mutation in either protein cause early-onset Parkinson’s disease.
Using biochemical, structural and cell-biological studies, we have arrived at a detailed molecular description of PINK1/Parkin mediated mitophagy, and now appreciate the mechanisms leading to PINK1 and Parkin activation. I will further discuss unpublished methods and tools that allow us to study ubiquitination in novel ways. This has led to a complete picture of what the actual mitophagy signal looks like.