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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Autophagy Assays for Biological Discovery and Therapeutic Development.
Noboru Mizushima,Leon Murphy +1 more
TL;DR: Both advantages and disadvantages of currently available methods to monitor autophagy are summarized and how these assays should be used in high-throughput screens to identify autophagic-modulating drugs and genes and the general features needed for biomarkers to assess Autophagy in humans are discussed.
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PINK1 and Parkin – mitochondrial interplay between phosphorylation and ubiquitylation in Parkinson's disease.
TL;DR: A critical overview of the key advances in the field is provided and the outstanding questions, including novel ways in which this knowledge could be exploited to develop therapies against Parkinson's disease are discussed.
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Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response
TL;DR: It is reported that pyoverdine translocates into the host, where it binds and extracts iron, and the host detects this damage via a conserved mitochondrial surveillance pathway mediated by the ESRE network.
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Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease
TL;DR: This study provides strong evidence that disturbance of Ca2+ homeostasis and mitochondrial abnormalities in Pompe disease represent early changes in a complex pathogenetic cascade leading from a deficiency of a single lysosomal enzyme to severe and hard-to-treat autophagic myopathy.
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The Matrix Protein of Human Parainfluenza Virus Type 3 Induces Mitophagy that Suppresses Interferon Responses.
TL;DR: It is shown that matrix protein (M) of HPIV3 translocates to mitochondria and interacts with Tu translation elongation factor mitochondrial (TUFM), which is sufficient to induce mitophagy by bridging autophagosomes and mitochondria.
References
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
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