Copper - a novel stimulator of autophagy

Hans Zischka; Guido Kroemer

doi:10.15698/cst2020.05.218

Copper - a novel stimulator of autophagy

Cell Stress. 2020 Apr 24;4(5):92-94. doi: 10.15698/cst2020.05.218.

Authors

Hans Zischka^{1

2}, Guido Kroemer^{3

4

5

6

7}

Affiliations

¹ Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
² Technical University Munich, School of Medicine, Institute of Toxicology and Environmental Hygiene, Biedersteiner Strasse 29, 80802 Munich, Germany.
³ Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
⁴ Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.
⁵ Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
⁶ Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
⁷ Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Toxic copper accumulation causes Wilson disease, but trace amounts of copper are required for cellular and organismal survival. In a recent paper Tsang et al. (Nat Cell Biol, doi: 10.1038/s41556-020-0481-4) demonstrate that copper binds with high affinity to a designated interaction site in the pro-autophagic kinases ULK1 and ULK2. Chelation of copper or genetic deletion of this copper-binding site inhibits autophagy and hence reduces the fitness of KRAS-induced cancers. These findings suggest that copper chelation might constitute a novel therapeutic intervention on autophagy-dependent malignancies.

Keywords: MEK1; ULK1; ULK2; Wilson disease; autophagy; cancer; copper.

Publication types

Comment