Crucial protein boosts infection risk in mitochondrial disease
Professor Fisher with Dr Francione in the La Trobe laboratory.
Mitochondria and Legionella infections in the social amoeba.
In a world first, Melbourne scientists have discovered that a certain protein is responsible for stimulating infection in mitochondrially diseased cells.
The research involved the stress signaling protein AMPK. It was carried out by scientists from La Trobe University, Deakin University and the University of Turin, Italy, in an organism called a slime mould – Dictyostelium discoideum – whose cells are strikingly similar to human cells.
Team leader, La Trobe Professor of Microbiology, Paul Fisher says the findings are a significant step forward in understanding more about the role of AMPK in the way mitochondrial disease damages cells.
Mitochondria are tiny compartments within cells that produce most of their energy. Mitochondrial diseases result from a reduced capacity of the mitochondria to generate energy. AMPK acts as a stress alarm that stimulates production of more mitochondria in an attempt to boost the person’s energy.
Professor Fisher says mitochondrial disease was initially thought to be a rare disorder. However recent research has demonstrated that it may affect one in 250 Australians.
AMPK also shuts down some of the cell’s energy consuming functions in an attempt to conserve energy. This shutdown can damage the cells. Mitochondrial defects also play a central role in major neurodegenerative diseases like Alzheimer’s, Parkinson’s and Huntington’s.
Infected with Legionella
The new research is published in the September issue of the scientific journal Disease Models and Mechanisms. Professor Fisher explains that the scientists first created mitochondrial disease in the slime mould before infecting it with Legionella, a bacterium that causes a severe form of pneumonia.
‘In her PhD research in my laboratory, Dr Lisa Francione found that the Legionella grew faster inside the diseased cells than inside healthy cells and that this was caused by the activity of AMPK,’ says Professor Fisher.
‘It is the first time that scientists have been able to show that the stress-signal associated with mitochondrial disease facilitates the growth and reproduction of the lunginfecting bacteria Legionella.’
The report titled Legionella pneumophila multiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells was written by Lisa Francione, Paige Smith, Sandra Accari, Paul Bokko and Paul Fisher from La Trobe, Salvatore Bozzaro from the University of Turin, Italy, and Peter Beech and Philip Taylor from Deakin University.
Professor Fisher says striking similarities exist between simple organisms like Dictyostelium and humans that allow scientists to use them to understand human disease.
Dictyostelium is a free-living amoeba whose life cycle makes it easy to manipulate and useful to study disease processes. Like humans, it can be infected by Legionella and quickly responds by producing a host of metabolism-associated proteins.
Another similarity between humans and Dictyostelium is that both use AMPK as an internal sensor to coordinate energy synthesis with energy needs.
However, unlike humans, researchers can deliberately create genetic diseases in Dictyostelium and infect it with germs like Legionella in a controlled environment. This makes it possible to determine the influence of pre-existing genetic diseases on the course of infection.