Zinc and autophagy

Biometals. 2014 Dec;27(6):1087-96. doi: 10.1007/s10534-014-9773-0. Epub 2014 Jul 11.


Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated. Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria. Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy / drug effects
  • Autophagy / genetics
  • Autophagy / physiology*
  • Carrier Proteins / metabolism
  • Endosomes / metabolism
  • Ethanol / pharmacology
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Inflammasomes / metabolism
  • Inflammation / metabolism
  • Lipid Metabolism
  • Lysosomes / metabolism
  • Mammals / physiology
  • Zinc / pharmacology
  • Zinc / physiology*


  • Carrier Proteins
  • Inflammasomes
  • Ethanol
  • Zinc