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Transition metal homeostasis: from yeast to human disease

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Abstract

Transition metal ions are essential nutrients to all forms of life. Iron, copper, zinc, manganese, cobalt and nickel all have unique chemical and physical properties that make them attractive molecules for use in biological systems. Many of these same properties that allow these metals to provide essential biochemical activities and structural motifs to a multitude of proteins including enzymes and other cellular constituents also lead to a potential for cytotoxicity. Organisms have been required to evolve a number of systems for the efficient uptake, intracellular transport, protein loading and storage of metal ions to ensure that the needs of the cells can be met while minimizing the associated toxic effects. Disruptions in the cellular systems for handling transition metals are observed as a number of diseases ranging from hemochromatosis and anemias to neurodegenerative disorders including Alzheimer’s and Parkinson’s disease. The yeast Saccharomyces cerevisiae has proved useful as a model organism for the investigation of these processes and many of the genes and biological systems that function in yeast metal homeostasis are conserved throughout eukaryotes to humans. This review focuses on the biological roles of iron, copper, zinc, manganese, nickel and cobalt, the homeostatic mechanisms that function in S. cerevisiae and the human diseases in which these metals have been implicated.

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Acknowledgments

This work was supported in part by a grant from the Canadian Institute for Health Research (to RTAM). MRB was supported by a graduate fellowship from the Strategic Training Program in Transfusion Science funded by CIHR and the Heart & Stroke Foundation of Canada.

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  1. Department of Biochemistry and Molecular Biology, Centre for Blood Research, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T1Z3, Canada

    Mark R. Bleackley & Ross T. A. MacGillivray

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Correspondence to Ross T. A. MacGillivray.

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Bleackley, M.R., MacGillivray, R.T.A. Transition metal homeostasis: from yeast to human disease. Biometals 24, 785–809 (2011). https://doi.org/10.1007/s10534-011-9451-4

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