Research Grant
[Cite as https://purl.org/au-research/grants/nhmrc/280613]Researchers: Prof Nick Hoogenraad (Principal investigator)
Brief description Mitochondria are essential organelles providing the cell with essential molecules and being the source of oxidative energy in the cell. They are at the centre of many clinical conditions, ranging from genetic to common neurological diseases and other conditions related to ageing. We have been defining the way in which mammalian cells respond to the accumulation of unfolded proteins within the mitochondrial compartment and have found this produces what we have called the Mitochondrial Stress Response, a process that results in the selective upregulation of a suite of genes encoding mitochondrial stress proteins. This application deals with the question of the consequences to the cell of the creation of proteolytic environment. We have found that the two major proteases of the mitochondrion are upregulated and that this results in a marked increase in the rate of degradation of mitochondrial proteins. We aim to determine the specific roles of individual proteases in this process and the consequences of this proteolysis on the efflux of peptides from the mitochondria. This question has important medical implications, as one of the consequences of defects in mitochondrial function is the loss of cells from the affected tissue. We will also address the question of how mitochondrial biogenesis is regulated. We have recently found that the cytosolic molecular chaperone Hsp90 is required for protein import into mitochondria in mammalian cells. Since Hsp90 has hitherto been shown to be a key regulatory component in the steroid hormone and tyrosine kinase signalling pathways, this finding raises the possibility that protein import and thereby mitochondrial biogenesis may be regulated via the involvement of Hsp90.
Funding Amount $AUD 432,750.00
Funding Scheme NHMRC Project Grants
Notes Standard Project Grant
- nhmrc : 280613
- PURL : https://purl.org/au-research/grants/nhmrc/280613