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Redox biochemistry of mammalian metallothioneins

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Abstract

Metallothionein (MT) is a generic name for certain families of structurally rather variable metal-binding proteins. While purely chemical or biological approaches failed to establish a single physiologic function for MTs in any species, a combination of chemical and biological approaches and recent progress in defining the low but significant concentrations of cytosolic free zinc(II) ions have demonstrated that mammalian MTs function in cellular zinc metabolism in specific ways that differ from conventional knowledge about any other metalloprotein. Their thiolate coordination environments make MTs redox-active zinc proteins that exist in different molecular states depending on the availability of cellular zinc and the redox poise. The zinc affinities of MTs cover a range of physiologic zinc(II) ion concentrations and are modulated. Oxidative conditions make more zinc available, while reductive conditions make less zinc available. MTs move from the cytosol to cellular compartments, are secreted from cells, and are taken up by cells. They provide cellular zinc ions in a chemically available form and participate in cellular metal muffling: the combination of physiologic buffering in the steady state and the cellular redistribution and compartmentalization of transiently elevated zinc(II) ion concentrations in the pre-steady state. Cumulative evidence indicates that MTs primarily have a redox-dependent function in zinc metabolism, rather than a zinc-dependent function in redox metabolism.

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Abbreviations

ABD-F:

7-Fluorobenz-2-oxa-1,3-diazole-4-sulfonamide

MT:

Metallothionein

MTF-1:

Metal response element (MRE)-binding transcription factor-1

PTP-1B:

Protein tyrosine phosphatase-1B

SDH:

Sorbitol dehydrogenase

T:

Thionein

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Authors and Affiliations

  1. King’s College London, Metal Metabolism Group, Diabetes and Nutritional Sciences Division, School of Medicine, Franklin–Wilkins Bldg., 150 Stamford St., London, SE1 9NH, UK

    Wolfgang Maret

  2. Department of Biochemistry, School of Biomedical and Health Sciences, King’s College London, London, UK

    Wolfgang Maret

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  1. Wolfgang Maret
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Correspondence to Wolfgang Maret.

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This article is part of a JBIC special issue on metallothioneins.

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Maret, W. Redox biochemistry of mammalian metallothioneins. J Biol Inorg Chem 16, 1079–1086 (2011). https://doi.org/10.1007/s00775-011-0800-0

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