Connecting iron regulation and mitochondrial function in Cryptococcus neoformans.
Journal
Current opinion in microbiology
ISSN: 1879-0364
Titre abrégé: Curr Opin Microbiol
Pays: England
ID NLM: 9815056
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
30
01
2019
revised:
04
04
2019
accepted:
05
04
2019
pubmed:
16
5
2019
medline:
29
7
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
Iron acquisition is essential for the proliferation of microorganisms, and human pathogens such as the fungus Cryptococcus neoformans must use sophisticated uptake mechanisms to overcome host iron sequestration. Iron is of particular interest for C. neoformans because its availability is an important cue for the elaboration of virulence factors. In fungi, extracellular iron is taken up through high affinity, low affinity, siderophore-mediated, and heme uptake pathways, and the details of these mechanisms are under active investigation in C. neoformans. Following uptake, iron is transported to intracellular organelles including mitochondria where it is used in heme biosynthesis and the synthesis of iron-sulfur (Fe-S) cluster precursors. One Fe-S cluster binding protein of note is the monothiol glutaredoxin Grx4 which has emerged as a master regulator of iron sensing in C. neoformans and other fungi through its influence on the expression of proteins for iron uptake or use. The activity of Grx4 likely occurs through interactions with Fe-S clusters and transcription factors known to control expression of the iron-related functions. Although the extent to which Grx4 controls the iron regulatory network is still being investigated in C. neoformans, it is remarkable that it also influences the expression of many genes encoding mitochondrial functions. Coupled with recent studies linking mitochondrial morphology and electron transport to virulence factor elaboration, there is an emerging appreciation of mitochondria as central players in cryptococcal disease.
Identifiants
pubmed: 31085406
pii: S1369-5274(18)30090-0
doi: 10.1016/j.mib.2019.04.002
pmc: PMC6842668
mid: NIHMS1527015
pii:
doi:
Substances chimiques
Glutaredoxins
0
Iron-Sulfur Proteins
0
Trace Elements
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
7-13Subventions
Organisme : NIAID NIH HHS
ID : R01 AI053721
Pays : United States
Organisme : CIHR
ID : MOP-13234
Pays : Canada
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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