Chapter 10 Metallothionein: Structure and regulation

Abstract

Although ample data suggests that MT is involved in the regulation and interactions with metals and oxidants, its physiological role remains elusive. MT knockout models reveal little about the physiological significance of MT, since the animals develop and appear normal. However, it has been observed that MT knockout mice are obese 10 This suggests a link between MT and energy balance. The animals are hyperphagic and deposit lipids at a high rate. Thus MT may prevent accumulation of those energy stores. Recently it was suggested that MT could inhibit the respiratory chain by donating Zn 89 , resulting in lowered ATP and free radical production. This mechanism may explain how MT prevents obesity, while at the same time being able to regulate the levels of free radicals. Interestingly, defects in energy metabolism have been correlated to longevity in yeast, C. elegans and Drosophila 81 and also to high MT expression in C. elegans 8 . Since aging is correlated to an increased amount of free radicals 11 , a possible role for MT is to function as a regulator of energy balance, thereby prolonging life. The correlation between age, energy expenditure, Zn status, free radical production and MT expression are fascinating future prospects.