Neuronal functionality and vitality rely on a functional network of mitochondria, making dysfunctions and defects in mitochondrial quality control a key contributor in neurodegenerative diseases such as Parkinson’s Disease. A central quality control pathway named mitophagy promotes damaged mitochondria degradation upon a multitude of different signals, thereby protecting cells from inflammatory effects of damaged mitochondria. The kinase PINK1 and the ubiquitin ligase Parkin mediate the most studied form of mitophagy. Mutations in this pathway drive autosomal recessive juvenile onset of Parkinson’s Disease, and therefore have been an important target to halt Parkinson’s Disease progression. Improving mitochondrial health in dopaminergic neurons, which are prone to die in Parkinson’s Disease, may slow or halt the progression of Parkinson’s Disease.
Recent developments in stem cell biology have led to generation of 3D midbrain derived organoids that can be used as disease relevant models to study the function of Parkinson’s Disease genes. We established an imaging framework to analyse PINK1/Parkin mitophagy in midbrain derived organoids. This platform serves to better understand the biology of mitophagy in Parkinson’s disease, as well as the interplay between dopaminergic neurons and astrocytes during mitochondrial stress.