Role of Aif1 in regulation of cell death under environmental stress in Candida albicans

Yeast. 2016 Sep;33(9):493-506. doi: 10.1002/yea.3167. Epub 2016 May 30.

Abstract

Apoptosis-inducing factor (AIF) is a conserved flavoprotein localized in the mitochondria, inducing apoptosis after translocation into the nucleus. However, its role in the important fungal pathogen, Candida albicans, remains to be investigated. In this study, we find that the C. albicans AIF protein Aif1, similar to its homologues in other organisms, is localized at the mitochondria and translocated into the nucleus under apoptosis-inducing conditions. Moreover, deletion of AIF1 causes attenuated apoptosis in this pathogen under apoptosis-inducing conditions, such as the treatment of 2 mm H2 O2 , 10 mm acetic acid or 0.08 mg/l caspofungin, and its overexpression enhances this process. Interestingly, treatment with high levels of these agents leads to reversed sensitivity of aif1Δ/Δ and the overexpression strain AIF1ov. In addition, the virulence of C. albicans is not affected by deletion or overexpression of AIF1. Hence, C. albicans Aif1, as a mitochondria-localized protein, plays a dual role in the regulation of cell death under different concentrations of the stress-caused agents. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: Candida albicans; apoptosis; apoptosis-inducing factor; mitochondrial membrane potential; reactive oxygen species.

MeSH terms

  • Acetic Acid / pharmacology
  • Antifungal Agents / pharmacology
  • Apoptosis
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • Candida albicans / pathogenicity
  • Caspofungin
  • Cell Death / physiology*
  • Echinocandins / pharmacology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic / physiology
  • Gene Expression Regulation, Fungal / physiology
  • Hydrogen Peroxide / pharmacology
  • Lipopeptides / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • Phylogeny
  • Reactive Oxygen Species
  • Stress, Physiological*
  • Virulence

Substances

  • Antifungal Agents
  • Echinocandins
  • Fungal Proteins
  • Lipopeptides
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • NADH, NADPH Oxidoreductases
  • Caspofungin
  • Acetic Acid