Moonlighting mitochondria: understanding why mitochondria import and metabolise methylated amino acids
Supervisors:
Thomas MacVicar, School of Cancer Sciences, University of Glasgow
Colin Adrain, Queen’s University Belfast
Summary:
This collaborative PhD project between the MacVicar (Glasgow) and Adrain (Belfast) labs will explore the impact of mitochondrial methylated amino acid (MeAA) metabolism on cellular and organismal health. These modified amino acids are present in the diet and arise upon the breakdown of methylated proteins. While MeAAs are linked to conditions like heart disease and kidney failure, the importance of mitochondria in the handling of these amino acids is unclear. We hypothesise that mitochondrial control of MeAA metabolism is a major determinant of cell growth and response to stress.
This project, which builds on our recent discoveries, will investigate how mitochondrial import of a MeAA called trimethyllysine impacts the cell’s ability to handle fatty acids. The consequence of genetic and pharmacological inhibition of MeAA metabolism on lipid homeostasis and cell health will be measured via high-throughput imaging, lipid assays and state-of-the-art Omics approaches, including spatial metabolomics and lipidomics. The successful candidate will also explore the broader impact of MeAA metabolism on physiology by applying a range of in vivo techniques, including metabolic phenotyping. Together, with the support of world leading research facilities, these in vitro and in vivo approaches will help define the physiological contexts that depend on mitochondrial MeAA metabolism.