Issue 11, 2018

Iron-sensing is governed by mitochondrial, not by cytosolic iron–sulfur cluster biogenesis in Aspergillus fumigatus

Abstract

Microorganisms have to adapt their metabolism to the requirements of their ecological niche to avoid iron shortage as well as iron toxicity. Therefore, mechanisms have been evolved to tightly regulate iron uptake, consumption, and detoxification, which depend on sensing the cellular iron status. In the facultative anaerobic yeast Saccharomyces cerevisiae, iron-sensing depends on mitochondrial (ISC) but not cytosolic iron–sulfur cluster assembly (CIA), while in mammals further processing of an ISC product via CIA is required for sensing of the cellular iron state. To address the question of how the obligatory aerobic mold Aspergillus fumigatus senses the cellular iron state, mutant strains allowing the downregulation of ISC and CIA were generated. These studies revealed that: (i) Nfs1 (Afu3g14240) and Nbp35 (Afu2g15960), which are involved in ISC and CIA, respectively, are essential for growth; (ii) a decrease in ISC (Nfs1 depletion) but not CIA (Nbp35 depletion) results in a transcriptional iron starvation response, (iii) a decrease in, ISC as well as CIA, increases the chelatable iron pool, accompanied by increased iron toxicity and increased susceptibility to oxidative stress and phleomycin. In agreement with ISC being essential for iron-sensing, a decrease in mitochondrial iron import by deletion of the mitochondrial iron importer MrsA resulted in an iron starvation response. Taken together, these data underline that iron-sensing in A. fumigatus depends on ISC but not CIA. Moreover, depletion of the glutathione pool via generating a mutant lacking γ-glutamylcysteine synthase, GshA (Afu3g13900), caused an iron starvation response, underlining a crucial role of glutathione in iron-sensing in A. fumigatus.

Graphical abstract: Iron-sensing is governed by mitochondrial, not by cytosolic iron–sulfur cluster biogenesis in Aspergillus fumigatus

Supplementary files

Article information

Article type
Paper
Submitted
13 Way 2018
Accepted
09 Dit 2018
First published
05 Xim 2018
This article is Open Access
Creative Commons BY license

Metallomics, 2018,10, 1687-1700

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