Mechanisms of Proteostasis in Mitochondria
Proteases provide spatio-temporal control of biological processes by destroying critical protein components at precise times. Understanding how proteases select proteins substrates from a crowded cellular environment and catalyze their degradation is crucial to making sense of how biological processes are regulated. Controlled protein degradation is essential for maintaining the function of mitochondria. ATP production, calcium signalling, fatty acid metabolism, and programmed cell death are all regulated by a mitochondrial proteome that is largely encoded in the nucleus and imported into the organelle.
A major topic of interest in the lab is the role that energy-dependent proteases belonging to the AAA+ family of enzymes play in sculpting the mitochondrial proteome. We are focused on determining the rules that govern substrate selection by these proteases and the conformational fluctuations that allow them to capture energy from ATP hydrolysis to be used in protein degradation.