BGU, The National Institute for Biotechnology in the Negev (NIBN) and US National Institutes of Health researchers have identified the path mitochondrial DNA use to exit cells in order to trigger autoimmune diseases and how to block that escape route. The researchers have demonstrated their concept in Lupus and their findings were reported in Science on Friday.
Prof. Varda Shoshan-Barmatz (pictured above) of the Department of Life Sciences and the founding Director of The National Institute for Biotechnology in the Negev (NIBN), discovered a unique mechanism involving the mitochondrial protein voltage-dependent anion channel (VDAC1) in the exit of mitochondrial factors such as pro-cell death proteins and mitochondrial DNA (mtDNA) that trigger some autoimmune diseases.
When VDAC1 is over-expressed, as found in several diseases, a large pore composed of several VDAC1 units is formed, allowing the release of pro-cell death factors and mtDNA.
Prof. Shoshan-Barmatz has developed a molecule that inhibits cell death and restores mitochondrial functions associated with several diseases. That novel molecule prevents the formation of the large pore caused by VDAC1 overexpression and thereby prevents the exit of these factors from the mitochondria. Without the release of these factors, cell death in diseases such as Alzheimer's and Parkinson's diseases, or mtDNA release like in Lupus is avoided.
“Our breakthrough is identifying a new pathway for the exit of mitochondrial DNA that we can either trigger under controlled conditions or inhibit using our novel molecule that we specifically developed to prevent the formation of this pathway,” says Prof. Shoshan-Barmatz.
“Since the results thus far with lupus have been so promising, we believe that the molecule will be beneficial with regards to other diseases such as Alzheimer’s, Crohn’s and ulcerative colitis - as our preliminary results already support,” she adds.
Lupus is a chronic autoimmune disease that can attack various parts of the body. According to the Lupus Foundation, there are five million cases around the world. Prof. Varda Shoshan-Barmatz in collaboration with a group from NIH, headed by Dr. Jay Chung, have had remarkable success in lupus mouse models so far and are beginning to take the next steps towards other diseases.
mtDNA has also been found in the plasma of patients of other autoimmune diseases such as Colitis and Crohn's diseases. This gives rise to new hope that this VDAC1-modulating molecule will lead to more therapies in an expanding list of other diseases that are associated with cell death or release of DNA from the mitochondria.