Sterol Composition Modulates the Response of Saccharomyces cerevisiae to Iron Deficiency.

Tania Jordá,Nicolas Rozès,Sergi Puig

doi:10.3390/jof7110901

Abstract

Iron is a vital micronutrient that functions as an essential cofactor in multiple biological processes, including oxygen transport, cellular respiration, and metabolic pathways, such as sterol biosynthesis. However, its low bioavailability at physiological pH frequently leads to nutritional iron deficiency. The yeast Saccharomyces cerevisiae is extensively used to study iron and lipid metabolisms, as well as in multiple biotechnological applications. Despite iron being indispensable for yeast ergosterol biosynthesis and growth, little is known about their interconnections. Here, we used lipid composition analyses to determine that changes in the pattern of sterols impair the response to iron deprivation of yeast cells. Yeast mutants defective in ergosterol biosynthesis display defects in the transcriptional activation of the iron-acquisition machinery and growth defects in iron-depleted conditions. The transcriptional activation function of the iron-sensing Aft1 factor is interrupted due to its mislocalization to the vacuole. These data uncover novel links between iron and sterol metabolisms that need to be considered when producing yeast-derived foods or when treating fungal infections with drugs that target the ergosterol biosynthesis pathway.

Highlights

Given that sterols contribute to membrane fluidity and ergosterol biosynthesis is an iron-dependent metabolic pathway, we decided to address whether changes in ergosterol biosynthesis influence the response of yeast to iron depletion
We first checked the activation of several iron regulon genes implicated in iron uptake (FET3, FTR1, and ARN2) in an erg4∆ mutant, which lacks the final step in ergosterol synthesis
These results suggest that ergosterol biosynthesis is important for the appropriate expression of the iron regulon in response to iron starvation

Summary

Introduction

Iron is an indispensable element for the large majority of living organisms because it functions as an essential cofactor in oxygen transport, respiration, and many metabolic processes, including lipid biosynthesis. Iron deficiency is a widely extended nutritional disorder affecting humans (predominantly children and women), animals, and crops [1,2]. Strategies to prevent and treat human iron deficiency include diet diversification, iron supplementation, and fortification of food with iron [3]. Yeast itself is consumed as a food supplement because it is especially rich in vitamins, proteins, and fiber. Iron-enriched yeasts can be used to prevent and ameliorate iron deficiency symptoms in animals and humans [4,5,6]

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