Roles of metallothionein in cellular metabolism

The metal-binding protein metallothionein (MT) is thought to play a physiol ogical role in Zn and Cu homeostasis and may donate or sequester these esse ntial metals on enzymes and transcription factors. However, the production of healthy MT knockout mice demonstrates that MT is not essential for survi val, growth or reproduction. Nevertheless, it appears to protect against so me 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 bein g observed in some different types of proliferating cells. This suggests a nuclear function for the protein during cell division, with possible modula tory effects on growth and development. Indeed, some MT knock-out mice beco me 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 wit h reference to work on genetically modified cells and animals.