text: Mutations that affect the functioning of the integrated stress response may have debilitating effects on cells. For example, cells lacking the ATF4 gene are unable to elicit proper gene expression in response to stressors. This results in cells exhibiting issues with amino acid transport, glutathione biosynthesis and oxidative stress resistance. When a mutation inhibits the functioning of PERK, endogenous peroxides accumulate when the cell experiences endoplasmic reticulum stress. In mice and humans lacking PERK, there have been observed destruction of secretory cells undergoing high endoplasmic reticulum stress.