title: Loss of iron triggers PINK1/Parkin-independent mitophagy.
abstract: 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.
authors.affiliation: MRC-Protein Phosphorylation and Ubiquitylation Unit, and.
authors.forename: George F G
authors.initials: GF
authors.lastname: Allen
authors.forename: Rachel
authors.initials: R
authors.lastname: Toth
authors.forename: John
authors.initials: J
authors.lastname: James
authors.forename: Ian G
authors.initials: IG
authors.lastname: Ganley
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D000090463:Iron Deficiencies; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063306:Mitophagy; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D007502:Iron Chelating Agents; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein