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DOI: 10.3390/ijms18061237

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Citation for published version (APA): Krel, A., & Maret, W. (2017). The functions of metamorphic metallothioneins in zinc and copper metabolism. International Journal of Molecular Sciences, 18(6), [1237]. https://doi.org/10.3390/ijms18061237

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Download date: 29. Sep. 2021 International Journal of Molecular Sciences

Review The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism

Artur Kr˛ezel˙ 1 and Wolfgang Maret 2,* 1 Department of Chemical Biology, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland; [email protected] 2 Division of Diabetes and Nutritional Sciences, Department of Biochemistry, Faculty of Life Sciences and Medicine, King’s College London, 150 Stamford Street, London SE1 9NH, UK * Correspondence: [email protected]; Tel.: +44-020-7848-4264; Fax: +44-020-7848-4195

Academic Editor: Eva Freisinger Received: 25 April 2017; Accepted: 3 June 2017; Published: 9 June 2017

Abstract: Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn2+, the loading of exocytotic vesicles with zinc species, and the control of Zn2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn2+ and Cu+ match the biological requirements for controlling—binding and delivering—these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn2+ and Cu+. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.