Researchers on the Universities of Bonn and Osnabrück have discovered a protein whose defect causes motor disorders in flies. The protein had also previously been present in human patients with Parkinson’s disease. Up to now, nevertheless, it was not known what function it has within the cell. The study now provides a solution to this query. The work, by which the University Hospital Aachen was also involved, has now been published within the journal Science Advances.

Of their study, the research groups checked out a protein called Creld. A study from Bonn had recently been capable of reveal that Creld plays a vital role in the event of the center in mammals. “We wanted to seek out out exactly what the protein does,” explains Dr. Margret Helene Bülow, a lecturer on the LIMES Institute of the University of Bonn.

For this purpose, the researchers studied fruit flies of the genus Drosophila, which that they had genetically modified in such a way that they can not form Creld. Within the animals, the center rate was slowed in a characteristic way – an indication of energy deficiency. In addition they exhibited severe motor disorders. The ability plants of the cell, the mitochondria, are accountable for providing energy. Their malfunction can lead to the death of nerve cells which might be accountable for motor function in humans. The clinical picture is generally known as Parkinson’s disease.

“So Creld may play a vital role not only in impaired heart function, but in addition in Parkinson’s disease,” says Dr. Nicole Kucharowski of the LIMES Institute, who, along along with her colleague Marie Paradis, conducted a key a part of the experiments within the study. “The findings of a recent evaluation are consistent with this. It suggests that Creld production is usually reduced in Parkinson’s patients.” But just how Creld could be related to Parkinson’s was puzzling: The protein shouldn’t be present in mitochondria in any respect. It could possibly be detected exclusively in a widely branched network of tubes that serves to supply various molecules within the cell – the endoplasmic reticulum (ER). How can it interfere with the function of cellular power plants from there?

Pesticide suspected of causing Parkinson’s disease

To search out out, the researchers administered small amounts of a pesticide to healthy fruit flies (i.e., people who can form Creld). It comprises the lively ingredient rotenone, which is suspected of triggering Parkinson’s disease in humans. Rotenone acts directly within the mitochondria by inhibiting a key step in energy production. After administration of the pesticide, the flies showed motor disorders much like those of the Creld mutants. “We also found that their mitochondria are fairly often involved with the ER,” Bülow explains.

In further experiments, the researchers were capable of show that certain classes of lipids are transported from the ER to the mitochondria during this contact. These so-called phospholipids rekindle the step in energy production that’s inhibited by rotenone. With assistance from the ER, the mitochondria attempt to ramp up the energy supply again in this manner. “And the supply of Creld appears to be crucial for this transfer of phospholipids,” Bülow points out. “In flies that can’t form Creld, phospholipids accumulate within the contact sites between ER and mitochondria. So that they do not get transported to the mitochondria, but accumulate.”

Creld increases energy production within the cell

Creld is due to this fact necessary for increasing energy production within the cell. That is according to the statement that Drosophila mutants without Creld produce hardly any hydrogen peroxide of their mitochondria – this can be a molecule produced as a waste material through the work of the ability plants. Hydrogen peroxide can damage cells. Until now, it was thought that it was produced in excessive amounts in individuals with Parkinson’s or that it was not adequately disposed of. This could regularly poison the nerve cells accountable for motor function.

It is feasible, nevertheless, that one other effect might cause their demise – namely, the chronic undersupply of energy triggered by damage to or underproduction of Creld. “It is a thesis that we now need to analyze further,” says Bülow, who’s a member of the Transdisciplinary Research Area “Life and Health” on the University of Bonn.

The present success can be the results of a successful cooperation. As an illustration, essential parts of the work were carried out on the University of Osnabrück. Dr. Julia Sellin, who originally helped initiate the study, has also recently moved to the University Hospital in Aachen. “The collaboration with Prof. Dr. Christoph Thiele from the Cluster of Excellence Immunosensation2 here on the University of Bonn also went extremely well,” stresses Bülow.

Source:

Journal reference:

Marie Paradis et al.: The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity; Science Advances; https://doi.org/10.1126/sciadv.abo0155