Loss of iron triggers PINK1/Parkin‐independent mitophagy
TLDR
A mitophagy pathway is identified and characterized, the induction of which could prove beneficial as a potential therapy for several neurodegenerative diseases in which mitochondrial clearance is advantageous.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.read more
Citations
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Selective autophagy: The new player in the fight against neurodegenerative diseases?
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TL;DR: VAMP7 participates in autophagosome formation by supporting Atg9a functions that contribute to maintenance of mitochondrial quality, and forms a SNARE complex with Syntaxin16 and SNAP-47, which may cause fusions of Atg 9a-resident vesicles during autophosome formation.
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Induced Pluripotent Stem Cell Neuronal Models for the Study of Autophagy Pathways in Human Neurodegenerative Disease
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References
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
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