Lack of DNA helicase Pif1 disrupts zinc and iron homoeostasis in yeast

María Guirola, Lina Barreto, Ayelen Pagani, Miriam Romagosa, Antonio Casamayor, Silvia Atrian, Joaquín Ariño

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

The Saccharomyces cerevisiae gene PIF1 encodes a conserved eukaryotic DNA helicase required for both mitochondrial and nuclear DNA integrity. Our previous work revealed that a pif1Δ strain is tolerant to zinc overload. In the present study we demonstrate that this effect is independent of the Pif1 helicase activity and is only observed when the protein is absent from the mitochondria. pif1Δ cells accumulate abnormal amounts of mitochondrial zinc and iron. Transcriptional profiling reveals that pif1Δ cells under standard growth conditions overexpress aconitase-related genes. When exposed to zinc, pif1Δ cells show lower induction of genes encoding iron (siderophores) transporters and higher expression of genes related to oxidative stress responses than wild-type cells. Coincidently, pif1Δ mutants are less prone to zinc-induced oxidative stress and display a higher reduced/oxidized glutathione ratio. Strikingly, although pif1Δ cells contain normal amounts of the Aco1 (yeast aconitase) protein, they completely lack aconitase activity. Loss of Aco1 activity is also observed when the cell expresses a non-mitochondrially targeted form of Pif1. We postulate that lack of Pif1 forces aconitase to play its DNA protective role as a nucleoid protein and that this triggers a domino effect on iron homoeostasis resulting in increased zinc tolerance. © The Authors Journal compilation © 2010 Biochemical Society.
Original languageEnglish
Pages (from-to)595-605
JournalBiochemical Journal
Volume432
DOIs
Publication statusPublished - 15 Dec 2010

Keywords

  • Aconitase
  • Iron homoeostasis
  • Pif1
  • Saccharomyces cerevisiae
  • Zinc homoeostasis

Fingerprint Dive into the research topics of 'Lack of DNA helicase Pif1 disrupts zinc and iron homoeostasis in yeast'. Together they form a unique fingerprint.

Cite this