Scientists at Yale have discovered how mitochondrial DNA defects cause maternally inherited deafness. They focused on a specific mutation that occurs in a gene that codes for RNA in mitochondrial ribosomes that generate a protein needed for cellular respiration. Cell lines with this mutation are prone to cell death due to the enhancement of a normal chemical modification of RNA. Researchers discovered that it is reactive oxygen molecules produced by the defective mitochondria that lead to the gene expression that causes cell death. When they genetically depleted the protein responsible for cell death, they were able to restore hearing in mice. “Mitochondrial diseases are complicated because different tissues are affected in often unpredictable ways. Defining the molecular mechanism underlying death of only a specific subset of cells in the inner ear is a major step toward unraveling this complexity,” said Nuno Raimundo, first author of the study.