Regulation of mitochondrial Turnover

Energy represents one of the most fundamental parameters in physiology and with respect to energy homeostasis, mitochondria are crucial organelle because they provide the majority of this energy under the form of adenosine triphosphate (ATP). To produce this ATP, mitochondria use different energy sources which are metabolized through a complex network. Together with this energy production, mitochondrial metabolism generates a variety of essential metabolites and it also controls homeostasis of signalling ions and molecules such as calcium, reactive oxygen species or neurotransmitters. Accordingly, mitochondria are pivotal structures for the cell metabolism but also for the global cell health.

Mitochondrial metabolic functions occur mainly in mitochondrial inner compartments: the mitochondrial matrix and inner membrane. These compartments are surrounded by a second membrane, the outer mitochondrial membrane. Despite this embedded localization, these metabolic activities must be constantly and finely orchestrated to fit the availability of substrates and the physiological needs.

Proteomic data from the literature as well as our own proteomic studies reveal that many mitochondrial metabolic proteins are ubiquitinylated. However, their implication in the regulation of the mitochondrial metabolism is still unknown. The aim of our project is to dissect the role played by the ubiquitin proteasome system UPS regarding the mitochondrial energy metabolism.

To achieve this aim, we have defined three specific objectives:

1. To characterize the mitochondrial ubiquitome and the UPS-dependent turnover of intra-mitochondrial proteins.
2. To identify and characterize mitochondrial E3 ubiquitin ligases.
3. To define the physiological consequences resulting from the UPS-dependent regulation of intramitochondrial proteins.


Contributing Members

Giovanni Bénard [CR]
Julie Lavie [PostDoc]
Harmony De Belvalet [Tech]
Claude Lalou [IR]

National and International Collaborations:

Plateforme de Protéomique de Bordeaux (Jean-William Dupuy)
Metatoul- Analyses Métabolomiques (INRA-Toulouse)