Copper - a novel stimulator of autophagy.

Hans Zischka,Guido Kroemer

doi:10.15698/cst2020.05.218

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.

Highlights

In Wilson disease (WD), a steadily copper pile-up has long been thought to elicit omnipresent toxic oxidative stress, sealing cellular and organismal fate
Chelation of copper or genetic deletion of this copper-binding site inhibits autophagy and reduces the fitness of KRAS-induced cancers. These findings suggest that copper chelation might constitute a novel therapeutic intervention on autophagy-dependent malignancies
These findings strongly suggest copper binding to act as a novel posttranscriptional modification of proteins that play critical roles in cellular signaling

Summary

Introduction

In WD, a steadily copper pile-up has long been thought to elicit omnipresent toxic oxidative stress, sealing cellular and organismal fate. Chelation of copper or genetic deletion of this copper-binding site inhibits autophagy and reduces the fitness of KRAS-induced cancers.

Results

Conclusion