Molecular basis of mitochondrial Complex I deficiency, the most common energy generation disorder

Funded Activity Summary

Oxygen is needed by every cell in the body to burn fuels (ie sugar, fat and protein) in small power plants inside each cell called mitochondria. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause a range of degenerative diseases later in life, particularly affecting brain, muscle and heart. In most cases we do not have any effective treatments. A major problem in understanding mitochondrial energy generation disorders is that the genetic causes are incredibly diverse. So far more than 20 genes have been shown to cause mitochondrial disorders, and it is likely that over one hundred more genes remain to be discovered. In addition to the regular genes that cause these and other genetic disorders, mitochondria are unique in carrying 37 extra genes located in a different part of the cell away from the rest of the human genome, and inherited only from the mother. This grant focuses on the most common energy generation disorder, known as Complex I deficiency. Complex I requires 43 separate components to be assembled together in order to work properly, but mutations in the 43 genes encoding these components are not present in most patients. We believe that the most common problems will be in genes involved in assembling the 43 components rather than in the components themselves. We will use a number of methods to pinpoint where in the genome the causative genes are located and then home in on the exact changes in the genes that cause disease. Identifying these genes will allow us to improve future diagnosis and prevention of mitochondrial disease. Understanding the basic biology may also allow us to develop new methods of treatment. Recent studies suggest that milder mitochondrial problems also contribute to a range of more common diseases such as diabetes and Parkinson disease, so any new treatments could potentially have wide application.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $515,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Genetics Not Elsewhere Classified

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

cell biology | gene mapping | inherited metabolic diseases | mitochondria | mitochondrial diseases: infant, child and adult | mitochondrial genetics | molecular basis of disease | molecular genetics | neurodegenerative disease | neuromuscular diseases

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