The intracellular compartmentation of essential and toxic metals is of intense scientific interest because of its potential for adding to our understanding of both normal homeostatic mechanisms for metals and of the mechanisms which underlie metal-induced cell injury. High-affinity metal-binding proteins, lysosomes, and precipitates such as inclusion bodies or concretions, play major roles in the regulation of divalent-metal cation bioavailability. The contribution of a given compartment toward metal homeostasis is dependent upon the level exposure, cell type, organ, species, and life cycle of the organism. Toxic metals may move between these compartments, but the rates and determinants of such exchanges have not been characterized. Available data clearly indicate that sequestration of toxic metals in these specialized compartments can produce profound disturbances in the subcellular handling of essential metals. Further studies of the mechanisms by which metals partition and/or transfer among these compartments are essential to understand and predict toxicity of this important class of toxic agents.
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