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The many highways for intracellular trafficking of metals

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Abstract

Metal ions such as copper and manganese represent a unique problem to living cells in that these ions are not only essential co-factors for metalloproteins, but are also potentially toxic. To aid in the homeostatic balance of essential but toxic metals, cells have evolved with a complex network of metal trafficking pathways. The object of such pathways is two-fold: to prevent accumulation of the metal in the freely reactive form (metal detoxification pathways) and to ensure proper delivery of the ion to target metalloproteins (metal utilization pathways). Much of what we currently know regarding these complex pathways of metal trafficking has emerged from molecular genetic studies in baker's yeast, Saccharomyces cerevisiae. In this review, we shall briefly highlight the current understanding of factors that function in the trafficking and handling of copper, including copper detoxification factors, copper transporters and copper chaperones. In addition, very recent findings on the players involved in manganese trafficking will be presented. The goal is to provide a paradigm for the intracellular handling of metals that may be applied in a more general sense to metals that serve essential functions in biology.

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Abbreviations

CTR:

cell surface transporter

GSH:

glutathione

MCF:

mitochondrial carrier family

mito:

mitochondria

MT:

metallothionein

SOD:

superoxide dismutase

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Acknowledgements

Much of the work described in this review was supported by the Johns Hopkins University NIEHS center and by NIH grants GM 50016 and ES 08996 to V.C.C.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Laran T. Jensen & Valeria C. Culotta

  2. Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Edward Luk & Valeria C. Culotta

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  1. Edward Luk
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  2. Laran T. Jensen
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  3. Valeria C. Culotta
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Corresponding author

Correspondence to Valeria C. Culotta.

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Luk, E., Jensen, L.T. & Culotta, V.C. The many highways for intracellular trafficking of metals. J Biol Inorg Chem 8, 803–809 (2003). https://doi.org/10.1007/s00775-003-0482-3

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