Scientists identify protein with a crucial role in cell death

Ageing, and the processes of deterioration that go with it, are largely attributable to cells that die off in a controlled manner. Therefore, gaining better understanding of this controlled cell death is very important in the fight against deterioration diseases like dementia.

In this light, researchers from the Flanders Interuniversity Institute for Biotechnology (VIB) connected to the K.U.Leuven, in collaboration with researchers from the Dulbecco-Telethon Institute hosted by the Veneto Institute of Molecular Medicine in Padua (Italy), have now discovered the function of the PARL protein. By studying mice that are unable to produce PARL, the researchers have discovered the significance of this protein in controlled cell death. An important step toward a good understanding of the ageing processes and of diseases like Parkinson's disease.

The cells' energy suppliers
Every living thing is composed of cells. There are a number of different cell types (brain cells, for example), each with its own particular function. To be able to perform their work, cells need energy. And this is what the mitochondria − which convert oxygen into the necessary energy − are responsible for. Given this vital function, scientists have suspected that the inner workings of a cell depend largely on how the mitochondria function. Therefore, it has been suspected that poorly functioning mitochondria can, among other things, lead to a disturbance in brain cells and thus contribute to Parkinson's disease.

A noble stranger...
This starting assumption brought two top researchers together: Bart De Strooper, who has extensive experience in Alzheimer research and is thus also interested in the causes of Parkinson's disease, and Luca Scorrano, who specializes in the functioning and effect of mitochondria. They set out to study PARL, a protein thought to interact with Presenilin, one of the major players in Alzheimer's disease. Previous research had already indicated that the link between PARL and Presenilin is negligible. It was understood that PARL is important to the cell's mitochondria, but the protein's particular function has remained unknown for a long time.

'Knock-out' mice
To obtain insight into PARL's function, the researchers used mice − called 'knock-out' mice − that were no longer able to produce this protein. These mice deteriorated very rapidly − losing muscular strength after only 4 weeks, which greatly reduced their capacity for breathing − and, after 8 to 12 weeks, they died. Thus, a lack of PARL leads to weakening of (muscle) cells, a phenomenon that also occurs in the normal ageing process. This result spurred the researchers on to find out the function of PARL.

Controlled cell death
During our lifetime, cells die off in a controlled manner − a process called apoptosis. In addition to supplying energy, mitochondria also ensure the integration and amplification of apoptosis signaling in the cell. From the research of De Strooper and Scorrano, it turns out that PARL is a key to initiating apoptosis in the mitochondria. Although the mitochondria of the knock-out mice have a normal development and are able to convert oxygen into energy, they have apparently lost their protection against apoptosis, and so the cells die off more quickly. Therefore, PARL plays a crucial role in the cells' dying off process and, consequently, probably also in the origin of diseases of ageing, like Parkinson's disease.

Source : VIB, Flanders Interuniversity Institute of Biotechnology