Roles of metallothionein in cellular metabolism

The metal-binding protein metallothionein (MT) is thought to play a physiological role in Zn and Cu homeostasis and may donate or sequester these essential metals on enzymes and transcription factors. However, the production of healthy MT knockout mice demonstrates that MT is not essential for survival, growth or reproduction. Nevertheless, it appears to protect against some effects of Zn deficiency and also the toxicity of heavy metals, oxidants and a wide range of stress factors. It shows notable induction during cell proliferation with marked and usually transitory nuclear localisation being observed in some different types of proliferating cells. This suggests a nuclear function for the protein during cell division, with possible modulatory effects on growth and development. Indeed, some MT knock-out mice become obese but it is not yet clear if this phenotype is caused by lack of MT. The cellular localisation and functions of MT-I and MT-II are reviewed with reference to work on genetically modified cells and animals.