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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Journal ArticleDOI
Multitasking guardian of mitochondrial quality: Parkin function and Parkinson’s disease
TL;DR: Parkin E3 ubiquitin ligase mutations are one of the most common causes of early-onset Parkinson's disease as discussed by the authors, and the role of the parkin protein product in the cellular processes related to mitochondrial function is discussed.
Journal ArticleDOI
Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment.
Sanjay Mehta,Sanjay Mehta,Josué Pérez-Santiago,Todd Hulgan,Tyler R C Day,Jill S. Barnholtz-Sloan,Haley Gittleman,Scott Letendre,Ronald J. Ellis,Robert K. Heaton,Stephanie M. Patton,Jesse D. Suben,Donald Franklin,Debralee Rosario,David B. Clifford,Ann C. Collier,Christina M. Marra,Benjamin B. Gelman,Justin C. McArthur,Allen McCutchan,Susan Morgello,David M. Simpson,James R. Connor,Igor Grant,Asha R. Kallianpur,Asha R. Kallianpur +25 more
TL;DR: CSF cell-free mtDNA levels were associated with HIV RNA and ART status, as well as with biomarkers of iron transport and VEGF, a growth factor with known effects on mitochondrial integrity and autophagy, and with inflammation- and iron-related biomarkers in CSF.
Journal ArticleDOI
FBXL4 deficiency increases mitochondrial removal by autophagy.
David Alsina,David Alsina,Oleksandr Lytovchenko,Oleksandr Lytovchenko,Aleksandra Schab,Ilian Atanassov,Florian A. Schober,Florian A. Schober,Min Jiang,Camilla Koolmeister,Camilla Koolmeister,Anna Wedell,Anna Wedell,Robert W. Taylor,Anna Wredenberg,Anna Wredenberg,Anna Wredenberg,Nils-Göran Larsson,Nils-Göran Larsson,Nils-Göran Larsson +19 more
TL;DR: The results presented here show that FBXL4 prevents mitochondrial removal via autophagy and that loss ofFBXL4 leads to decreased mitochondrial content and mitochondrial disease.
Journal ArticleDOI
Novel p53-dependent anticancer strategy by targeting iron signaling and BNIP3L-induced mitophagy
Nastasia Wilfinger,Shane Austin,Barbara Scheiber-Mojdehkar,Walter Berger,Siegfried Reipert,Monika Praschberger,Jakob Paur,Robert Trondl,Bernhard K. Keppler,Christoph C. Zielinski,Karin Nowikovsky +10 more
TL;DR: Targeting BNIP3L in wild-type p53 colon cancer cells is a novel anticancer strategy activating iron depletion signaling and the mitophagy-related cell death pathway.
Journal ArticleDOI
PINK1 and Parkin: team players in stress-induced mitophagy
TL;DR: Mitochondria are highly vulnerable organelles based on their complex biogenesis, entailing dependence on nuclear gene expression and efficient import strategies, and certain types of stress-induced mitophagy are regulated by the mitochondrial kinase PINK1 and the E3 ubiquitin ligase Parkin, which are both linked to autosomal recessive Parkinson's disease.
References
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