Copper induces cell death by targeting lipoylated TCA cycle proteins.
Science
; 375(6586): 1254-1261, 2022 03 18.
Article
in En
| MEDLINE
| ID: mdl-35298263
ABSTRACT
Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, is unknown. Here, we show in human cells that copper-dependent, regulated cell death is distinct from known death mechanisms and is dependent on mitochondrial respiration. We show that copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death. These findings may explain the need for ancient copper homeostatic mechanisms.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Citric Acid Cycle
/
Copper
/
Regulated Cell Death
Limits:
Animals
/
Humans
Language:
En
Journal:
Science
Year:
2022
Document type:
Article
Affiliation country:
United States