The malfunction of peroxisome has an impact on the oxidative stress sensitivity in Candida albicans

Fungal Genet Biol. 2016 Oct:95:1-12. doi: 10.1016/j.fgb.2016.07.010. Epub 2016 Jul 27.

Abstract

The peroxisome plays an essential role in eukaryotic cellular metabolism, including β-oxidation of fatty acids and detoxification of hydrogen peroxide. However, its functions in the important fungal pathogen, C. albicans, remain to be investigated. In this study, we identified a homologue of Saccharomyces cerevisiae peroxisomal protein Pex1 in this pathogen, and explored its functions in stress tolerance. Fluorescence observation revealed that C. albicans Pex1 was localized in the peroxisomes, and its loss led to the defect in peroxisome formation. Interestingly, the pex1Δ/Δ mutant had increased tolerance to oxidative stress, which was neither associated with the Cap1 pathway, nor related to the altered distribution of catalase. However, under oxidative stress, the pex1Δ/Δ mutant showed increased expression of autophagy-related genes, with enhanced cytoplasm-to-vacuole transport and degradation of the autophagy markers Atg8 and Lap41. Moreover, the double mutants pex1Δ/Δatg8Δ/Δ and pex1Δ/Δatg1Δ/Δ, both of which were defective in autophagy and peroxisome formation, showed remarkable attenuated tolerance to oxidative stress. These results indicated that autophagy is involved in resistance to oxidative stress in pex1Δ/Δ mutant. Taken together, this study provides evidence that the peroxisomal protein Pex1 regulates oxidative stress tolerance in an autophagy-dependent manner in C. albicans.

Keywords: Autophagy; Cap1; Oxidative stress; Peroxisome; Pex1.

MeSH terms

  • AAA Proteins
  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • ATPases Associated with Diverse Cellular Activities / physiology*
  • Autophagy / genetics
  • Autophagy / physiology
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Candida albicans / metabolism*
  • Candida albicans / pathogenicity
  • Catalase / metabolism
  • Cell Cycle Proteins / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Deletion
  • Hydrogen Peroxide / metabolism
  • Macrophages / microbiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology*
  • Mutation
  • Oxidative Stress / physiology*
  • Peroxisomes / enzymology*
  • Peroxisomes / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / physiology*
  • Stress, Physiological
  • Vacuoles / metabolism
  • Virulence

Substances

  • Basic-Leucine Zipper Transcription Factors
  • CAP1 protein, Candida albicans
  • Cell Cycle Proteins
  • Fungal Proteins
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Hydrogen Peroxide
  • Catalase
  • AAA Proteins
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, S cerevisiae