The molecular mechanisms of cuproptosis and its relevance to cardiovascular disease

Recently, cuproptosis has been demonstrated to be a new non-apototic cell death mode that is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis is distinct from known cell death modes such as apoptosis, necrosis, pyroptosis, or ferroptosis. Excessive copper induces cuproptosis by promoting protein toxic stress reactions via copper-dependent anomalous oligomerization of lipoylation proteins in the tricarboxylic acid (TCA) cycle and reducing iron-sulfur cluster protein levels. Ferredoxin1 (FDX1) promotes dihydrolipoyl transacetylase (DLAT) lipoacylation and abates iron-sulfur cluster proteins by reducing Cu2+ to Cu+, inducing cell death. Copper homeostasis depends on…

• NN
  National Natural Science Foundation of China

  Awards: 82000209, 82100439
• SM
  Southwest Medical University

  Award: KeyME-2021–05
• SP
  Sichuan Province Science and Technology Support Program