Protein Alarm for Mitochondria Identified by Australian Researcher

'Thanks to this research,' Brumby said, 'we now have a completely new understanding of how mitochondrial disease is caused - from a signalling disorder in the cells, rather than a fundamental energy insufficiency as was previously thought.'

Advertisement

'The finding has important implications for the development of drug therapies to treat the many different forms of mitochondrial disease, as well as for most major neurodegenerative disorders.'

Mitochondria are responsible for creating more than 90% of the energy needed by the body to sustain life and support growth. When they fail, less and less energy is generated within the cell. Cell injury and even cell death follow. If this process is repeated throughout the body, whole systems begin to fail, and the life of the person in whom this is happening is severely compromised. The disease primarily affects children, but adult onset is becoming more and more common.

Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.

Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection.

Professor Fisher has shown in the laboratory that an energy-sensing protein, known as AMPK, is permanently activated in mitochondrially diseased cells. When energy supplies drop, it begins signalling and interfering with other signalling pathways, causing cell functions to shut down.

So far, Professor Fisher's work has used a type of amoeba called a slime mould (the scientific name is Dictyostelium discoideum, Dicty to its friends). Genetically inhibiting the production of the alarm protein suppressed all of the 'symptoms' of mitochondrial disease in Dicty.

'If we can suppress the symptoms in humans as well, this research may provide the first possibility of treating mitochondrial diseases,' Professor Fisher said.

About 1,000 people at any one time suffer from genetic defects of the mitochondria in Australia, resulting in a varied range of symptoms. More than 50 children develop these conditions annually and more than half die before adulthood.

'All of the major neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's also involve mitochondrial defects,' Professor Fisher said. 'They might also be turning on this alarm protein.' AMPK plays a 'smoke alarm' role to censor an impending energy crisis and to take remedial action.

'If there is an energy problem, the cell does not want to embark on division or processes that consume energy,' Professor Fisher said. 'So the protein switches them off before the situation becomes critical.' In healthy cells, energy supplies return to normal, as does cell functioning, but in diseased cells AMPK activity may trigger a permanent shut-down.

'In these cases, AMPK acts like an oversensitive smoke alarm that goes off every time you cook toast. Imagine if it locked every window and door to stop the fire spreading and turned off the electricity and gas. This is worse than the problem it tried to solve,' Professor Fisher said.

Source: Medindia
GPL/P