CCS and hepatocellular carcinoma: For example, yeast with mutated sod1 accumulate DNA mutations,35 and SOD1 knockout mice develop hepatocellular carcinoma, presumably as a result of oxidative damage of hepatocytes.36 Moreover, CCS expression is regulated by cellular Cu status; when Cu content decreases, CCS levels increase, and when Cu content is high, the degradation of CCS increases.37,38 Both CCS and SOD1 are localized in both the cytoplasm and mitochondrial intermembrane space (IMS), where they detoxify mitochondria-derived superoxides.39,40