# Copper induces cell death by targeting lipoylated TCA cycle proteins

“Copper induces cell death by targeting lipoylated TCA cycle proteins” (2022), by Peter Tsvetkov et al. Genetics and Biochemistry research paper. Original abstract below, unchanged. No free PDF was found.

- Authors: Peter Tsvetkov, Shannon Coy, Boryana Petrova, Margaret B. Dreishpoon, Ana Verma, Mai Abdusamad, Jordan Rossen, Lena M. Joesch-Cohen, Ranad Humeidi, Ryan D. Spangler et al.
- Published: March 17, 2022
- Field: Genetics and Biochemistry
- DOI: https://doi.org/10.1126/science.abf0529
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/9273333

## 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.

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