EASTBIO: Application of mitochondrial capture methods to uncover novel mitochondrial mechanisms

Molecular dissection of the protein kinase PINK1 and ubiquitin ligase Parkin, that are both mutated in Parkinson’s disease, has revealed a highly conserved mitochondrial quality control pathway found in nearly every cell type including neurons. Upon mitochondrial damage, activation of PINK1 and Parkin leads to ubiquitin-dependent removal of damaged mitochondria by autophagy (mitophagy). The intramitochondrial mechanisms of damaged mitochondria that are targeted for mitophagy are poorly understood. Our laboratory has been deploying powerful new methods to rapidly isolate mitochondria within minutes for biochemical and proteomic analysis. These methods have potential to uncover deep molecular insights into the early changes that occur within mitochondria following damage. The project will harness these methods and combine them with proteomics, metabolomics and lipidomics to determine the mitochondrial signatures of various types of mitochondrial damage and further extend this to understanding how mutations in disease-associated genes linked to mitochondrial disorders lead to mitochondrial dysfunction. The project will provide outstanding training in the latest methods to to study organelle biology as well as mass spectrometry.