Loss of iron triggers PINK1/Parkin-independent mitophagy

TY - JOUR

T1 - Loss of iron triggers PINK1/Parkin-independent mitophagy

AU - Allen, George F. G.

AU - Toth, Rachel

AU - James, John

AU - Ganley, Ian G.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84889100159

U2 - 10.1038/embor.2013.168

DO - 10.1038/embor.2013.168

M3 - Article

C2 - 24176932

SN - 1469-221X

VL - 14

SP - 1127

EP - 1135

JO - EMBO Reports

JF - EMBO Reports

ER -