Loss of iron triggers PINK1/Parkin‐independent mitophagy
| Autor: | Rachel Toth, Ian G. Ganley, John James, George F. G. Allen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
autophagy
PINK1 Biology Mitochondrion Bioinformatics medicine.disease_cause Biochemistry Parkin 03 medical and health sciences 0302 clinical medicine Mitophagy Genetics medicine Glycolysis Molecular Biology 030304 developmental biology 0303 health sciences Mutation Scientific Reports iron/mitophagy Autophagy Iron deficiency medicine.disease nervous system diseases 3. Good health Cell biology 030217 neurology & neurosurgery |
| Zdroj: | EMBO Reports |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.1038/embor.2013.168 |
| Popis: | Loss of iron triggers PINK1/Parkin-independent mitophagy 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. 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. |
| Databáze: | OpenAIRE |
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