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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Recent Advances in Iron Metabolism: Relevance for Health, Exercise, and Performance.
TL;DR: A hemoglobin-independent effect of iron on exercise capacity has been demonstrated in animal models and humans, and the tight link between erythropoiesis and iron metabolism is particularly relevant to sports physiology.
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Shedding light on mitophagy in neurons: what is the evidence for PINK1/Parkin mitophagy in vivo?
Nadia Cummins,Jürgen Götz +1 more
TL;DR: The evidence for a functional PINK1/Parkin mitophagy pathway in neurons is described, and how this pathway is affected in disease models are reviewed, including findings from in vitro models and more recent in vivo studies in flies and mice.
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Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration.
TL;DR: Therapeutic strategies targeting lysosomes and autophagic machinery have already been tested in several aging-related neurodegenerative diseases with promising results, suggesting that improving lysOSomal function could be similarly beneficial in preserving function in the aging brain.
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Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
TL;DR: In this article , the authors discuss mechanisms that regulate mitochondrial calcium uptake and release, the impact of LRRK2, PINK1, Parkin, beta-amyloid and glucocerebrosidase on mitochondrial calcium transporters, and the role of autophagic mitochondrial loss in axodendritic shrinkage.
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Mitochondrial stress management: a dynamic journey
TL;DR: This review will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage, including initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response, mitochondrial dynamics and elimination by mitophagy.
References
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
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