Understanding the role of cysteine in ferroptosis: progress & paradoxes

Cysteine is a conditionally essential amino acid required for the synthesis of proteins and many important intracellular metabolites. Cysteine depletion can trigger iron-dependent nonapoptotic cell death-ferroptosis. Despite this, cysteine itself is normally maintained at relatively low levels within the cell, and many mechanisms that could act to buffer cysteine depletion do not appear to be especially effective or active, at least in cancer cells. How do we reconcile these seemingly paradoxical features? Here, we describe the regulation of cysteine and its contribution to ferroptosis and speculate about how the levels of this amino acid are controlled to govern nonapoptotic cell death.

Automated summary

Cysteine is conditionally essential for protein synthesis and intracellular metabolites, and its depletion can trigger nonapoptotic cell death. Despite being normally maintained at low levels within cells, mechanisms to buffer cysteine depletion seem ineffective in cancer cells. The regulation of cysteine and its contribution to ferroptosis are discussed in this article.