Specific VDAC inhibitors: phosphorothioate oligonucleotides

VDAC channels are ancient, highly-conserved voltage-gated channels in the mitochondrial outer membrane. They are the pathways by which metabolites travel between the cytosol and mitochondria. They are involved in the apoptotic process and probably other functions as well. The lack of specific inhibitors has hampered research in the past but now phosphorothioate oligonucleotides can serve this function. These molecules were generated to be stable in the cytosol of cells but, unlike the oligonucleotides with the physiological phosphodiester linkage, these have the ability to bind to and block VDAC channels. They are potent, specific, and available commercially. At 1 microM concentration they block VDAC channels in mitochondria but do not affect the respiration complexes, the adenine nucleotide translocator or the ATP synthase.