Researchers identify crucial protein
In a world first, Melbourne scientists have discovered that the stress signaling protein AMPK is responsible for stimulating infection in mitochondrially diseased cells.
The research undertaken by scientists from La Trobe University, Deakin University and the University of Turin, Italy, was carried out in the slime mould (Dictyostelium discoideum) whose cells are strikingly similar to human cells.
Mitochondria and Legionella infections in the social amoeba.
‘We found that the Legionella grew faster inside the diseased cells than inside healthy cells and that this was caused by the activity of AMPK,’ said 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 lung-infecting bacteria Legionella,’ he said.
The findings are to be published in the September issue of the new scientific journal Disease Models and Mechanisms.
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. AMPK also shuts down some of the cell’s energy consuming functions in an attempt to conserve energy and 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.
Mitochondrial disease was initially thought to be a rare disorder. However recent research has demonstrated that mitochondrial disease may affect one in 250 Australians.
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 of La Trobe University, Salvatore Bozzaro of the University of Turin, Italy, and Peter Beech and Philip Taylor of Deakin University.
Striking similarities that exist between simple organisms like Dictyostelium and humans 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, Dictyostelium 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 preexisting genetic diseases on the course of infection.
Professor Paul Fisher
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