Candida albicans lacking the frataxin homologue: a relevant yeast model for studying the role of frataxin.

Abstract:

:We cloned the CaYFH1 gene that encodes the yeast frataxin homologue in Candida albicans. CaYFH1 was expressed in Deltayfh1 Saccharomyces cerevisiae cells, where it compensated for all the phenotypes tested except for the lack of cytochromes. Double DeltaCayfh1/DeltaCayfh1 mutant had severe defective growth, accumulated iron in their mitochondria, lacked aconitase and succinate dehydrogenase activity and had defective respiration. The reductive, siderophore and haem uptake systems were constitutively induced and the cells excreted flavins, thus behaving like iron-deprived wild-type cells. Mutant cells accumulated reactive oxygen species and were hypersensitive to oxidative stress, but not to iron. Cytochromes were less abundant in mutants than in wild-type cells, but this did not result from defective haem synthesis. The low cytochrome concentration in mutant cells was comparable to that of iron-deprived wild-type cells. Mitochondrial iron was still available for haem synthesis in DeltaCayfh1/DeltaCayfh1 cells, in contrast to S. cerevisaeDeltayfh1 cells. CaYFH1 transcription was strongly induced by iron, which is consistent with a role of CaYfh1 in iron storage. Iron also regulated transcription of CaHEM14 (encoding protoporphyrinogen oxidase) but not that of CaHEM15 (encoding ferrochelatase). There are thus profound differences between S. cerevisiae and C. albicans in terms of haem synthesis, cytochrome turnover and the role of frataxin in these processes.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Santos R,Buisson N,Knight SA,Dancis A,Camadro JM,Lesuisse E

doi

10.1111/j.1365-2958.2004.04281.x

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

507-19

issue

2

eissn

0950-382X

issn

1365-2958

pii

MMI4281

journal_volume

54

pub_type

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