Copper induces cell death by targeting lipoylated TCA cycle proteins.
Science
; 375(6586): 1254-1261, 2022 03 18.
Article
en 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ciclo del Ácido Cítrico
/
Cobre
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Muerte Celular Regulada
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article