Investigating the role of retromer in mitochondrial quality control (360G-Wellcome-203959_Z_16_A)

Mitochondria are highly versatile compartments that exist within eukaryotic cells. They perform a myriad of functions, but most importantly are tasked with producing energy at a rate that meets an incessant cellular demand, allowing cells to dynamically move, grow and divide in response to environmental cues. Energy production by mitochondria is intricately orchestrated by complex protein machineries acting in exquisite collaboration with one another. Importantly, dysfunction of mitochondria leads to cell death and is a hallmark of a range of human diseases, particularly neurodegenerative pathologies such as Alzheimer’s and Parkinson’s disease. As a result, cells have evolved several quality control mechanisms to ensure that damaged mitochondrial components are degraded before they pose a threat to cell viability. In the most recently discovered mechanism, damaged mitochondrial proteins are dynamically clustered together, then trafficked away from mitochondria and towards a separate part of the cell, the lysosome, where they are destroyed. In my PhD project, I will investigate which proteins are transported away from the mitochondria in this fashion, and the mechanistic details of how this occurs. This approach will reveal novel insights into a key aspect of mitochondrial biology, and could enhance our understanding of mitochondria in neurodegenerative disease.