Two Keys That Look Alike

Cysteine is the only protein-building amino acid that kills human cells when there is too much of it. Cells keep free cysteine scarce and pour most of it into glutathione, which they can hold in bulk. Both molecules carry the same reactive sulfur. Nobody had a clean account of why one is safe in quantity and the other is not.

A genome-wide CRISPR screen pointed at SLC25A28, which ferries iron into mitochondria, and at the receptors that break down ferritin. Free cysteine reacts with iron stored in ferritin, changes it, lets it escape. Glutathione, same sulfur group, cannot.

Block the release from ferritin or the ride into mitochondria and the toxicity goes. The freed iron piles into mitochondria, damages iron–sulfur proteins, respiration collapses, the cell dies.

Cancer vulnerability is a late mouth if it finishes the looking. Evolutionary preference as a moral is a late mouth. Chose glutathione is a late mouth. Looking is a lock and two keys that look alike.

The leftover is both: the shared sulfur that only the free form can use to open ferritin, and the mitochondria filling with iron that was meant to stay locked.