An adaptation to low copper in Candida albicans involving SOD Enzymes and the alternative oxidase

Chynna N. Broxton, Valeria L Culotta

Research output: Contribution to journalArticle

Abstract

In eukaryotes, the Cu/Zn superoxide dismutase (SOD1) is a major cytosolic cuproprotein with a small fraction residing in the mitochondrial intermembrane space (IMS) to protect against respiratory superoxide. Curiously, the opportunistic human fungal pathogen Candida albicans is predicted to express two cytosolic SODs including Cu/Zn containing SOD1 and manganese containing SOD3. As part of a copper starvation response, C. albicans represses SOD1 and induces the non-copper alternative SOD3. While both SOD1 and SOD3 are predicted to exist in the same cytosolic compartment, their potential role in mitochondrial oxidative stress had yet to be investigated. We show here that under copper replete conditions, a fraction of the Cu/Zn containing SOD1 localizes to the mitochondrial IMS to guard against mitochondrial superoxide. However in copper starved cells, localization of the manganese containing SOD3 is restricted to the cytosol leaving the mitochondrial IMS devoid of SOD. We observe that during copper starvation, an alternative oxidase (AOX) form of respiration is induced that is not coupled to ATP synthesis but maintains mitochondrial superoxide at low levels even in the absence of IMS SOD. Surprisingly, the copper-dependent cytochrome c oxidase (COX) form of respiration remains high with copper starvation. We provide evidence that repression of SOD1 during copper limitation serves to spare copper for COX and maintain COX respiration. Overall, the complex copper starvation response of C. albicans involving SOD1, SOD3 and AOX minimizes mitochondrial oxidative damage whilst maximizing COX respiration essential for fungal pathogenesis.

Original languageEnglish (US)
Article numbere0168400
JournalPLoS One
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2016

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Candida
Candida albicans
Copper
superoxide dismutase
copper
Starvation
Enzymes
enzymes
Respiration
cell respiration
Superoxides
starvation
superoxide anion
Manganese
Oxidoreductases
manganese
Electron Transport Complex IV
alternative oxidase
Eukaryota
Cytosol

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

An adaptation to low copper in Candida albicans involving SOD Enzymes and the alternative oxidase. / Broxton, Chynna N.; Culotta, Valeria L.

In: PLoS One, Vol. 11, No. 12, e0168400, 01.12.2016.

Research output: Contribution to journalArticle

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