Mitophagy And Mitochondrial Biogenesis In Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
Mutations in mitochondrial DNA and nuclear encoded mitochondrial genes cause mitochondrial disease, with one in every 250 Australians carrying a pathogenic mutation. In this project, we will further define the basic function of mitophagy (process that results in the recycling of defective mitochondria) and mitochondrial biogenesis (production of new mitochondria). Additionally, experimentally induced enhancement of mitophagy or biogenesis will be assessed as a potential therapy for patients with ....Mutations in mitochondrial DNA and nuclear encoded mitochondrial genes cause mitochondrial disease, with one in every 250 Australians carrying a pathogenic mutation. In this project, we will further define the basic function of mitophagy (process that results in the recycling of defective mitochondria) and mitochondrial biogenesis (production of new mitochondria). Additionally, experimentally induced enhancement of mitophagy or biogenesis will be assessed as a potential therapy for patients with mitochondrial disease.Read moreRead less
The Structure And Organization Of The Mitochondrial Genome In Health And Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$553,646.00
Summary
Mitochondrial DNA (mtDNA) mutations and mitochondrial dysfunction have been associated with a wide range of multi-system human diseases, although much remains to be learnt about molecular mechanisms in the pathogenesis of these diseases. Our goal is to understand how the expression of the mitochondrial DNA is regulated by mtDNA-binding proteins that will allow us to provide important insights into the molecular mechanisms of mitochondrial diseases.
Mitochondrial Damage Following Fetal Hypoxia Or Birth Asphyxia: Using Creatine To Preserve Mitochondrial Function
Funder
National Health and Medical Research Council
Funding Amount
$838,726.00
Summary
There is a need for a therapy that can be given before a mother gives birth to protect the baby should ‘oxygen starvation’ threaten the baby’s brain and other organs such as the heart, kidney, lungs, and the ability to breathe properly. We are suggesting that an increased intake of creatine is a very effective treatment against this threat, and its proven safety and ease of use recommends it for wide application, particularly in countries where the access to medical resources is poor.
Gene Discovery And Functional Studies To Reveal Mechanisms Underlying Mitochondrial Respiratory Chain Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$381,343.00
Summary
Mitochondrial respiratory chain disorders are a devastating group of disorders, potentially affecting any organ of the body, with no effective therapies currently available. The majority of these disorders have a childhood onset and the genetic basis for most of them is unknown. Identification of the genes responsible for these disorders in specific families would greatly improve the accuracy and usefulness of genetic counselling, and an understanding of their biology may assist the development ....Mitochondrial respiratory chain disorders are a devastating group of disorders, potentially affecting any organ of the body, with no effective therapies currently available. The majority of these disorders have a childhood onset and the genetic basis for most of them is unknown. Identification of the genes responsible for these disorders in specific families would greatly improve the accuracy and usefulness of genetic counselling, and an understanding of their biology may assist the development of effective therapies.Read moreRead less
Mitochondria are both the powerhouses and the poison cupboard of our cells. They have evolved from bacteria and still possess the ability to grow and divide. Unregulated mitochondrial division is seen in dying cells and in cells from patients with neurodegenerative diseases. We have identified new molecules involved in mitochondrial division and are investigating how they function in normal and unhealthy cells.
Fission, Fusion And Distribution Of Mitochondria In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Mitochondria are small cellular compartments that produce most of the cell's energy in the form of ATP. Mitochondria were once thought of as small bean-shaped organelles floating around in the cell, however it has become clear that this is not the case. Mitochondria are found as a network of tubules radiating from around the nucleus and they undergo constant changes in their shape through both fission and fusion events. Mitochondria are transported along microtubules which act as highways in the ....Mitochondria are small cellular compartments that produce most of the cell's energy in the form of ATP. Mitochondria were once thought of as small bean-shaped organelles floating around in the cell, however it has become clear that this is not the case. Mitochondria are found as a network of tubules radiating from around the nucleus and they undergo constant changes in their shape through both fission and fusion events. Mitochondria are transported along microtubules which act as highways in the cell so that they can be distributed to areas that require ATP or other functions particular to mitochondria such as their ability to regulate the release of calcium. In specialist cells, mitochondria are organised even further. Sperm cells contain mitochondria packed around the mid-piece of the flagellum so that ATP can be utilised directly for swimming. Mitochondria are also highly organised in muscle cells to supply ATP for movement while in pancreatic cells mitochondria at the cell's edge help to regulate the secretion of molecules such as insulin into the bloodstream. While we are beginning to understand the great importance of mitochondria to the cell, we are yet to work out how these organelles undergo the drastic morphological changes which are essential for cellular function. In this application, we plan to identify and characterise the proteins involved in the division of mitochodria and the movement of these organelles along the microtubule highways. Understanding the basic mechanisms of mitochondrial dynamics in tissue culture cells will provide valuable insights into mitochondrial segregation and specialisation in differentiated cells such as sperm, nerve, muscle and pancreatic cells, where such events are crucial for function.Read moreRead less
Understanding The Link Between Mitochondrial Biogenesis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$421,055.00
Summary
As the predominate energy producers of our cells, mitochondria are implicated in a variety of diseases. To function properly, these dynamic organelles rely on protein components that regulate their structure and distribution throughout the cell. My work aims to expand our knowledge of the way these components control mitochondrial shape and trafficking. By understanding the correlation between mitochondrial morphology and function, we will gain insight into related diseases.
Biogenesis Of Respiratory Chain Complex I And Analysis Of Assembly Defects In Patients With Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Complex I of the mitochondrial respiratory chain is a large assembly of protein subunits that is involved in the main production of cellular energy. Complex I is found in intracellular compartments termed mitochondria. The predicament for Complex I is that in order for it to be built, it requires 38 different proteins that are made in one place in the cell to be imported into mitochondria and then somehow joined together with the 7 other subunits that are made by mitochondria. This is clearly a ....Complex I of the mitochondrial respiratory chain is a large assembly of protein subunits that is involved in the main production of cellular energy. Complex I is found in intracellular compartments termed mitochondria. The predicament for Complex I is that in order for it to be built, it requires 38 different proteins that are made in one place in the cell to be imported into mitochondria and then somehow joined together with the 7 other subunits that are made by mitochondria. This is clearly a complicated procedure and we have little information on how its assembly is achieved. We do know however that mistakes in the assembly of Complex I do happen. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others present later causing a range of degenerative diseases, particularly affecting brain, muscle and heart. The most common defect in these patients is a loss in the activity of Complex I. Interestingly it seems that in most cases, the defect is not due to a mutation in one or more of the Complex I subunits and so we believe that such defects arise form accessory proteins that are involved in the construction of Complex I. The aim of this proposal is to investigate how Complex I is assembled and to identify and characterise accessory proteins. We will also analyse assembly defects by studying skin fibroblasts from patients. This work will aid in our understanding of not only how protein complexes are built, but how defects in their assembly can cause disease. This will not only be informative to families of affected individuals but may aid in future diagnosis and prevention of mitochondrial disease.Read moreRead less
Carolyn Sue is a neurologist and scientist investigating the role of disturbed mitochondrial function in human disease. Mitochondria play a key role in maintaining energy levels and the cell’s health. When this function is impaired, cells may degenerate or die, and thus cause human disease. Dr Sue’s research is aimed at seeking improved treatments to treat mitochondrial disease and to further understanding about how brain cells degenerate when the mitochondria fail.
Functional Genomic Analyses Of Mitochondrial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$577,001.00
Summary
Mitochondria produce most of the energy required by our bodies. Mutations in genes that make mitochondrial proteins cause mitochondrial dysfunction and lead to neurodegenerative and muscular diseases. We will identify mutations in mitochondrial genes in members of different Bulgarian and Gypsy families and discovery the mechanisms by which the mutations lead to disease.