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. A novel mitophagy assay uncovers a new PINK1/Parkin‐independent mitophagy pathway induced by a decrease in iron levels. This pathway is active in fibroblasts of Parkinson patients with Parkin mutations and could be exploited as a potential therapy.

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