reviewCell Death and DifferentiationFeb 8, 2023HYBRID OA

Cuproptosis: p53-regulated metabolic cell death?

Shanghai Medical College of Fudan University · Fudan University Shanghai Cancer Center · +1 more institution

PubMed
Indexed incrossrefpubmed

Abstract

Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells that utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with the lipoylated proteins of the tricarboxylic acid cycle, leading to the disulfide-bond-dependent aggregation of these lipoylated proteins, destabilization of the iron-sulfur cluster proteins, and consequent proteotoxic stress. Cancer cells prefer glycolysis (Warburg effect) to oxidative phosphorylation for producing intermediate metabolites and energy, thereby achieving resistance to cuproptosis. Interestingly, the tumor suppressor p53 is a crucial metabolic regulator that inhibits glycolysis and drives a…

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