"One of NCATS' goals is to develop, leverage and improve innovative technologies, such as RNAi screening, which is used in collaborations across NIH to increase our knowledge of gene function in the context of human disease," said Dr. Martin.
For this study, the researchers used RNAi to screen human cells to identify genes that help parkin tag damaged mitochondria. They found that at least four genes, called TOMM7, HSPAI1L, BAG4 and SIAH3, may act as helpers. Turning off some genes, such as TOMM7 and HSPAI1L, inhibited parkin tagging whereas switching off other genes, including BAG4 and SIAH3, enhanced tagging. Previous studies showed that many of the genes encode proteins that are found in mitochondria or help regulate a process called ubiquitination, which controls protein levels in cells.
Next the researchers tested one of the genes in human nerve cells. The researchers used a process called induced pluripotent stem cell technology to create the cells from human skin. Turning off the TOMM7 gene in nerve cells also appeared to inhibit tagging of mitochondria. Further experiments supported the idea that these genes may be new targets for treating neurological disorders.
"These genes work like quality control agents in a variety of cell types, including neurons," said Dr. Youle. "The identification of these helper genes provides the research community with new information that may improve our understanding of Parkinson's disease and other neurological disorders."
The RNAi screening data from this study are available in NIH's public database, PubChem, which any researcher may analyze for additional information about the role of dysf
|Contact: Christopher G Thomas|
NIH/National Institute of Neurological Disorders and Stroke