Control of mitochondrial energy metabolism by the ubiquitin/proteasome system. – Ubinergy

Mitochondria are important intracellular organelles which participate to the cellular health by providing energy for all biological functions. This metabolic function of mitochondria requires a fine regulation. Otherwise, the energy homoeostasis is altered which lead to severe physiological consequences. It is established that many proteins of mitochondrial metabolic network are ubiquitinated but it is unclear whether this ubiquitination is important for mitochondrial metabolism. To date, the molecular mechanisms, the implication of signaling pathways, the physiological relevance as well as the metabolic consequences to these ubiquitinations are unknown. Accordingly, the overall goal of our project is to decipher the link between the ubiquitin-dependent degradation in the mitochondrial energy metabolism. In the current application, we concentrate our investigations on two central questions:

Aim 1. Identification and characterization of mitochondrial ubiquitinated protein and E3 ubiquitin ligase under different energetic conditions.

Aim 2. Physiological relevance of the mitochondrial metabolism regulation by the UPS.

By tackling these two questions, our project will identify actors (ubiquitinated proteins, E3 ligases), point out the metabolic conditions mobilizing the UPS-dependent regulation, establish the involved molecular mechanism and finally, show its physiological importance. By addressing these questions, we expect to reveal an essential regulatory process for mitochondrial energy metabolism.