metallothionein

Metallothioneins are a family of low-molecular-weight, cysteine-rich metal-binding proteins found in many organisms. In humans, the MT gene family encodes several isoforms (MT-1 through MT-4). MT-1 and MT-2 are widely expressed; MT-3 is predominant in the brain; MT-4 is expressed in differentiated squamous epithelia.

They are small proteins (~61–68 amino acids) with a high cysteine content, lacking aromatic amino acids. They contain two metal-binding domains, α and β, that coordinate metal ions such as Zn2+, Cu+, and detoxify toxic metals like Cd2+ and Hg2+ through thiolate clusters.

Metallothioneins act as metal reservoirs and buffers that regulate intracellular availability of zinc and copper for metalloenzymes and transcription factors, and they also sequester and detoxify toxic metals. They can contribute to antioxidant defense by buffering redox-active metals and may influence cell growth and apoptosis.

Expression is controlled by metal-responsive transcription factor MTF-1 binding to metal response elements in MT gene promoters. They are induced by metal exposure (Zn, Cd, Cu), oxidative stress, glucocorticoids, and cytokines; tissue-specific expression patterns vary.

Metallothioneins serve as biomarkers of metal exposure and have potential roles in disease, including neurodegeneration and cancer, though causal relationships remain under study. They are also studied for therapeutic modulation of metal homeostasis and detoxification.