Mitochondria are organelles that provide cells with the energy they need to survive and grow. Mitochondrial health is crucial for cell function and is partly controlled by the enzyme DRP1 – a promising drug target for various neurological, oncological and cardiovascular disorders (Rosdah et al, doi:10.1016/j.pharmthera.2020.107594). DRP1 is regulated by phosphorylation events and we have recently discovered that DRP1 is activated by long chain fatty acid CoA esters (LCFA-CoAs) such as palmitoyl-CoA. We hypothesise thatDRP1-regulating kinases in the Ras-Raf-MEK-ERK pathway are also regulated by endogenous LCFA-CoAs, revealing a co-ordinated, metabolite-sensing capacity linking cellular nutrient availability to mitochondrial function.
Using a combination of biochemistry, cell biology, mass spectrometry and microscopy in a supportive and well-equipped environment, this exciting Honours project will generate new knowledge on metabolite sensing by central and fundamental signalling pathways.