Inhibition of Candida parapsilosis Fatty Acid Synthase (Fas2) Induces Mitochondrial Cell Death in Serum

Long Nam Nguyen, Gabriele Vargas Cesar, Giang Thi Thu Le, David L. Silver, Leonardo Nimrichter, Joshua D. Nosanchuk

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We have recently observed that a fatty acid auxotrophic mutant (fatty acid synthase, Fas2Δ/Δ) of the emerging human pathogenic yeast Candida parapsilosis dies after incubation in various media including serum. In the present study we describe the mechanism for cell death induced by serum and glucose containing media. We show that Fas2Δ/Δ yeast cells are profoundly susceptible to glucose leading us to propose that yeast cells lacking fatty acids exhibit uncontrolled metabolism in response to glucose. We demonstrate that incubation of Fas2Δ/Δ yeast cells with serum leads to cell death, and this process can be prevented with inhibition of protein or DNA synthesis, indicating that newly synthesized cellular components are detrimental to the mutant cells. Furthermore, we have found that cell death is mediated by mitochondria. Suppression of electron transport enzymes using inhibitors such as cyanide or azide prevents ROS overproduction and Fas2Δ/Δ yeast cell death. Additionally, deletion of mitochondrial DNA, which encodes several subunits for enzymes of the electron transport chain, significantly reduces serum-induced Fas2Δ/Δ yeast cell death. Therefore, our results show that serum and glucose media induce Fas2Δ/Δ yeast cell death by triggering unbalanced metabolism, which is regulated by mitochondria. To our knowledge, this is the first study to critically define a link between cytosolic fatty acid synthesis and mitochondrial function in response to serum stress in C. parapsilosis.

Original languageEnglish (US)
Article numbere1002879
JournalPLoS Pathogens
Volume8
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Fatty Acid Synthases
Candida
Cell Death
Yeasts
Serum
Glucose
Fatty Acids
Electron Transport
Mitochondria
Azides
Cyanides
Enzyme Inhibitors
Mitochondrial DNA
DNA
Enzymes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Inhibition of Candida parapsilosis Fatty Acid Synthase (Fas2) Induces Mitochondrial Cell Death in Serum. / Nguyen, Long Nam; Cesar, Gabriele Vargas; Le, Giang Thi Thu; Silver, David L.; Nimrichter, Leonardo; Nosanchuk, Joshua D.

In: PLoS Pathogens, Vol. 8, No. 8, e1002879, 08.2012.

Research output: Contribution to journalArticle

Nguyen, Long Nam ; Cesar, Gabriele Vargas ; Le, Giang Thi Thu ; Silver, David L. ; Nimrichter, Leonardo ; Nosanchuk, Joshua D. / Inhibition of Candida parapsilosis Fatty Acid Synthase (Fas2) Induces Mitochondrial Cell Death in Serum. In: PLoS Pathogens. 2012 ; Vol. 8, No. 8.
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