Mice homozygous for a missense point mutation show defective translation of the mitochondrial-encoded COX1 subunit and multi-systemic pathology affecting the heart, skeletal muscle, liver, and eye. Severe liver inflammation is linked to the highest reduction in complex IV activity, leading to increased mitochondrial ROS production and subsequent release of mitochondrial RNA into the cytoplasm of hepatocytes which triggers a type I interferon response and local inflammation in the liver.