The lysosome as a master regulator of iron metabolism

Trends Biochem Sci. 2021 Dec;46(12):960-975. doi: 10.1016/j.tibs.2021.07.003. Epub 2021 Aug 9.

Abstract

Intracellular iron fulfills crucial cellular processes, including DNA synthesis and mitochondrial metabolism, but also mediates ferroptosis, a regulated form of cell death driven by lipid-based reactive oxygen species (ROS). Beyond their established role in degradation and recycling, lysosomes occupy a central position in iron homeostasis and integrate metabolic and cell death signals emanating from different subcellular sites. We discuss the central role of the lysosome in preserving iron homeostasis and provide an integrated outlook of the regulatory circuits coupling the lysosomal system to the control of iron trafficking, interorganellar crosstalk, and ferroptosis induction. We also discuss novel studies unraveling how deregulated lysosomal iron-handling functions contribute to cancer, neurodegeneration, and viral infection, and can be harnessed for therapeutic interventions.

Keywords: cancer; ferroptosis; iron homeostasis; iron trafficking; neurodegenerative diseases; viruses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Death / physiology
  • Ferroptosis*
  • Iron / metabolism
  • Lysosomes / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Iron