Loss of iron triggers PINK1/Parkin-independent mitophagy

EMBO Rep. 2013 Dec;14(12):1127-35. doi: 10.1038/embor.2013.168. Epub 2013 Nov 1.


In this study, we develop a simple assay to identify mitophagy inducers on the basis of the use of fluorescently tagged mitochondria that undergo a colour change on lysosomal delivery. Using this assay, we identify iron chelators as a family of compounds that generate a strong mitophagy response. Iron chelation-induced mitophagy requires that cells undergo glycolysis, but does not require PINK1 stabilization or Parkin activation, and occurs in primary human fibroblasts as well as those isolated from a Parkinson's patient with Parkin mutations. Thus, we have identified and characterized a mitophagy pathway, the induction of which could prove beneficial as a potential therapy for several neurodegenerative diseases in which mitochondrial clearance is advantageous.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • HeLa Cells
  • Humans
  • Iron Chelating Agents / pharmacology*
  • Iron Deficiencies*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitophagy*
  • Mutation
  • Protein Kinases / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*


  • Iron Chelating Agents
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase