In the shadows of the membrane: A tale about how to beat the odds in cellular copper acquisition (360.3)

Critical for cellular function, ions of the transition metal copper need to reach multiple specific destinations inside cells in an efficient manner. That they do is taken for granted. Yet, how exactly does an ion of 11Å3 find binding sites of ~1000Å3 in a volume of 30,000,000,000,000Å3 that is accessible to diffusible species within the cytosol of even a small organism like yeast? The odds for this to happen through simple 3D‐random walks and diffusion are staggeringly low, and yet, live goes on as though this problem did not exist. Studying the mechanisms of cellular copper acquisition and distribution, we recently made the discovery that cells overcome the odds associated with targeted copper delivery by reducing the dimensionality of the search problem through exploitation of cellular membranes as scaffolding components. Specifically, our studies showed that cellular copper chaperones are able to associate with membranes and that this novel property of the chaperones is important for initial copper loading into the chaperone’s copper binding site. Taken together, our findings blend into a novel paradigm in which cellular membranes play a pivotal role in the intracellular distribution of copper ions.