Researchers based at the University of California, Los Angeles (UCLA) have discovered that problems with division of mitochondria, the cells energy source, can result in the onset of conditions such as Parkinson’s disease and have discovered another protein that can help correct this issue.
While the research is currently at the preclinical stage and was carried out in fruit flies, the team thinks it could lead to the development of new therapies targeting this pathway.
The gene DNM1L encodes the protein dynamin-related protein 1, which regulates mitochondria in human cells and controls whether or not fission, leading to more mitochondria, is needed or not. Mutations in this gene have been linked with neurodegenerative diseases such as Parkinson’s and if function is lost completely brain development is affected and most often leads to early death.
Ming Guo, a professor of neurology and of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, and colleagues wanted to find out whether the pathological effects of mutated DNM1L could be reversed.
As described in the journal Nature Communications, the researchers discovered that the Drosophila gene ‘Clueless’, CLUH in humans, is a regulator of dynamin-related protein 1 (Drp1).
“With a critically important pathway such as Drp1, there might be multiple proteins we could use to intervene and ultimately control Parkinson’s disease,” said Guo, in a press statement. “When we modified clueless in flies, symptoms analogous to Parkinson’s disease improved substantially.”
On further analysis, the team realized that the ability of the Clueless protein to control mitochondrial fission works in conjunction with the Drp1 protein and that normal amounts of both proteins are needed for levels of mitochondria organelles in the cells to stay at healthy levels. The CLUH protein helps translate DNM1L mRNA, found on the surface of mitochondria, into the Drp1 protein so mitochondrial fission can be triggered.
Guo and team now want to investigate if the DNM1L/CLUH pathway could be manipulated to help treat Parkinson’s disease in humans. “In the future, we hope to identify a mechanism with such precision that it only affects Parkinson’s disease, so patients can derive maximum benefit,” she said.