Copper ionophore elicits calpain-dependent paraptosis coincident with proteotoxic stress.

ABSTRACT: Copper is essential to all living organisms. However, too much copper is deleterious, and cellular copper content is therefore subject to tight control. Excess copper was recently found to perturb a set of metabolic enzymes in mitochondria, leading to the aggregation of these proteins and the demise of the cell. However, our understanding of the mechanism of copper-dependent cell death remains incomplete. Here, we report that copper ionophore (elesclomol)-induced cell death is calpain-dependent, featuring dilation of the endoplasmic reticulum along with perinuclear clustering of mitochondria. Moreover, elesclomol evoked proteotoxic stress, manifested as a disruption of ubiquitin and proteasome homeostasis, coupled with a conserved heat shock response. Overall, these results have shown that

SUBMITTER: Sae-Fung A 

PROVIDER: S-EPMC12837948 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature