World Library  

Add to Book Shelf
Flag as Inappropriate
Email this Book

Plos Genetics : Aconitase Causes Iron Toxicity in Drosophila Pink1 Mutants, Volume 9

By Lu, Bingwei

Click here to view

Book Id: WPLBN0003952777
Format Type: PDF eBook :
File Size:
Reproduction Date: 2015

Title: Plos Genetics : Aconitase Causes Iron Toxicity in Drosophila Pink1 Mutants, Volume 9  
Author: Lu, Bingwei
Volume: Volume 9
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Publication Date:
Publisher: Plos

Description : The PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase, and pink1 mutations cause early onset Parkinson’s disease (PD) in humans. Loss of pink1 in Drosophila leads to defects in mitochondrial function, and genetic data suggest that another PDrelated gene product, Parkin, acts with pink1 to regulate the clearance of dysfunctional mitochondria (mitophagy). Consequently, pink1 mutants show an accumulation of morphologically abnormal mitochondria, but it is unclear if other factors are involved in pink1 function in vivo and contribute to the mitochondrial morphological defects seen in specific cell types in pink1 mutants. To explore the molecular mechanisms of pink1 function, we performed a genetic modifier screen in Drosophila and identified aconitase (acon) as a dominant suppressor of pink1. Acon localizes to mitochondria and harbors a labile iron-sulfur [4Fe-4S] cluster that can scavenge superoxide to release hydrogen peroxide and iron that combine to produce hydroxyl radicals. Using Acon enzymatic mutants, and expression of mitoferritin that scavenges free iron, we show that [4Fe-4S] cluster inactivation, as a result of increased superoxide in pink1 mutants, results in oxidative stress and mitochondrial swelling. We show that [4Fe-4S] inactivation acts downstream of pink1 in a pathway that affects mitochondrial morphology, but acts independently of parkin. Thus our data indicate that superoxide-dependent [4Fe-4S] inactivation defines a potential pathogenic cascade that acts independent of mitophagy and links iron toxicity to mitochondrial failure in a PD–relevant model.


Click To View

Additional Books

  • Plos Genetics : Dna Damage, Homology-dir... (by )
  • Plos Genetics : Genome-wide Identificati... (by )
  • Plos Genetics : Genetics Meets Metabolom... (by )
  • Plos Genetics : Environmental Sex Determ... (by )
  • Plos Genetics : Understanding Mammalian ... (by )
  • Plos Genetics : Psoriasis Patients Are E... (by )
  • Plos Genetics : Antagonistic Regulation ... (by )
  • Plos Genetics : Nanoliter Reactors Impro... (by )
  • Plos Genetics : a Feed-forward Loop Coup... (by )
  • Plos Genetics : Evolutionary Conserved R... (by )
  • Plos Genetics : Post-embryonic Nerve-ass... (by )
  • Plos Genetics : the Environment Affects ... (by )
Scroll Left
Scroll Right


Copyright © World Library Foundation. All rights reserved. eBooks from World Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.