期刊
EMBO REPORTS
卷 14, 期 12, 页码 1127-1135出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2013.168
关键词
autophagy; iron/mitophagy; PINK1; Parkin
资金
- MRC Protein Phosphorylation and Ubiquitylation Unit DNA Sequencing Service
- Medical Research Council
- Wellcome Trust Strategic Award [097945/B/11/Z]
- Division of Signal Transduction Therapy Unit (AstraZeneca)
- Boehringer-Ingelheim
- GlaxoSmithKline
- Merck KGaA
- Janssen Pharmaceutica
- Pfizer
- Medical Research Council [MC_UP_A500_1019, MC_UU_12016/4] Funding Source: researchfish
- MRC [MC_UP_A500_1019, MC_UU_12016/4] Funding Source: UKRI
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.
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