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
More filters
Journal ArticleDOI
Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms.
Sonia Levi,Dario Finazzi +1 more
TL;DR: The most recent findings in the molecular mechanisms underlining the most common forms of NBIA are reviewed and their possible link with brain iron metabolism is analyzed.
Journal ArticleDOI
Emerging role of mitophagy in human diseases and physiology
Jee-Hyun Um,Jeanho Yun +1 more
TL;DR: A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment, and recent studies showing the involvement ofMitophagy in differentiation and development, suggest thatmitophagy may play a more active role in controlling cellular functions.
Journal ArticleDOI
The RAB11A-Positive Compartment Is a Primary Platform for Autophagosome Assembly Mediated by WIPI2 Recognition of PI3P-RAB11A
Claudia Puri,Mariella Vicinanza,Avraham Ashkenazi,M J Gratian,Qifeng Zhang,Carla F. Bento,Maurizio Renna,Fiona M. Menzies,David C. Rubinsztein +8 more
TL;DR: It is described that WIPI2 localizes to autophagic precursor membranes by binding RAB 11A, a protein that specifies recycling endosomes, and that PI3P is formed on RAB11A-positive membranes upon starvation.
Journal ArticleDOI
PINK1/Parkin mitophagy and neurodegeneration—what do we really know in vivo?
TL;DR: The evidence supporting PINK1/Parkin mitophagy in vivo and its causative role in neurodegeneration is reviewed, and outstanding questions for future investigations are outlined.
Journal ArticleDOI
Outstanding Questions in Mitophagy: What We Do and Do Not Know
TL;DR: The outstanding questions (and questions outstanding) in the field are discussed and the current understanding of mitophagy, the current challenges and the future directions to take are reflected.
References
More filters
Journal ArticleDOI
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
TL;DR: It is shown that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells and this recruitment promotes autophagy of damaged mitochondria and implicate a failure to eliminate dysfunctional mitochondira in the pathogenesis of Parkinson's disease.
Journal ArticleDOI
Sulforhodamine B colorimetric assay for cytotoxicity screening
TL;DR: The sulforhodamine B (SRB) assay is used for cell density determination, based on the measurement of cellular protein content, which is an efficient and highly cost-effective method for screening.
Journal ArticleDOI
Mitochondria: In Sickness and in Health
TL;DR: This work provides a current view of how mitochondrial functions impinge on health and disease and identifies mitochondrial dysfunction as a key factor in a myriad of diseases, including neurodegenerative and metabolic disorders.
Journal ArticleDOI
Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3
TL;DR: Using this method, evidence that overexpression of a dominant negative form of Rab7 prevented the fusion of autophagosomes with lysosomes is provided, suggesting that Rab7 is involved in this step.
Journal ArticleDOI
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
TL;DR: The role of reactive oxygen species (ROS) as signaling molecules in starvation‐induced autophagy is described and a cysteine residue located near the HsAtg4 catalytic site is specified as a critical for this regulation.