Researchers at the University of Bonn and the University of Osnabrück have discovered a protein whose defects cause movement disorders in flies. This protein was also previously discovered in human patients with Parkinson’s disease. However, so far, it has not been known what function it has in the cell. This study currently provides an answer to this question. This work, which also involved the University of Aachen Hospital, is currently being published in Science Advances.
In their study, the research group looked at a protein called cleld. Bonn’s work has recently been able to demonstrate that Clerdo plays an important role in the development of the mammalian heart. “We wanted to know exactly what proteins do,” explains Dr. Margret Helene Bülow, a lecturer at the University of Bonn’s LIMES Institute.
To this end, researchers studied the genus fruit fly. Drosophila, Genetically modified to prevent them from forming clelds. In animals, heart rate slowed in a characteristic way-a sign of lack of energy. They also showed severe movement disorders. Mitochondria, the power plant of cells, are responsible for supplying energy. Their dysfunction can lead to the death of nerve cells involved in human motor function. The clinical picture is known as Parkinson’s disease.
“Therefore, Clerdo may play an important role not only in cardiac dysfunction, but also in Parkinson’s disease,” said Nicole Kucharov of the LIMES Institute, who conducted an important part of the experiment with his colleague Marie Paradis. Dr. Ski says. study. “Recent analysis results are consistent with this, suggesting that patients with Parkinson’s disease often have reduced production of cleld.” But how cleld is associated with Parkinson’s disease. It was mysterious whether it was there. This protein is completely absent in mitochondria. It can only be detected in a network of widely branched tubes, the endoplasmic reticulum (ER), which help generate various molecules in the cell. How can you interfere with the functioning of the cellular power plant from there?
Pesticides that are thought to be the cause of Parkinson’s disease
To investigate, researchers administered small doses of pesticides to healthy fruit flies (ie, those capable of forming clelds). Contains the active ingredient rotenone, which is suspected of causing Parkinson’s disease in humans. Rotenone acts directly on mitochondria by blocking key steps in energy production. After administration of the pesticide, the flies showed a movement disorder similar to that of the Clerdo mutant. “We also found that mitochondria very often come into contact with ER,” Bülow explains.
In further experiments, researchers were able to show that certain classes of lipids were transported from the endoplasmic reticulum to mitochondria during this contact. These so-called phospholipids rekindle the steps of energy production that are inhibited by rotenone. With the help of the ER, mitochondria try to increase the energy supply again in this way. “And the availability of Creld seems to be important for this phospholipid migration,” Bülow points out. “In flies that cannot form clelds, phospholipids accumulate at the contact site between the endoplasmic reticulum and mitochondria, so phospholipids accumulate without being transported to mitochondria.”
Creld increases energy production in cells
Therefore, cleld is important for increasing energy production in the cell. This is consistent with the following observations: Drosophila Mutants without Creld produce very little hydrogen peroxide in the mitochondria. This is a molecule that is produced as waste during the work of a power plant. Hydrogen peroxide can damage cells. Previously, patients with Parkinson’s disease were thought to be overproduced or not properly disposed of. It gradually poisons the nerve cells involved in motor function.
However, another effect can cause their death-a chronic shortage of energy caused by damage to the cleld or underproduction. “This is a treatise that we need to investigate further,” says Bülow, a member of the University of Bonn’s interdisciplinary research area, Life and Health.
Current success is also the result of successful cooperation. For example, an important part of the work was carried out at the University of Osnabrück. Dr. Julia Zelin, who originally helped start the study, recently moved to a university hospital in Aachen. “The collaboration with Dr. Christoph Thiele of the Cluster of Excellence Immunosensation 2 here at the University of Bonn has also been very successful,” Bülow emphasizes.
Marie Paradis et al .: The ER protein Creld regulates ER-mitochondrial contact dynamics and respiratory complex 1 activity. Science Advances; https://doi.org/10.1126/sciadv.abo0155
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