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Candida albicans PPR proteins are required for the expression of respiratory Complex I subunits

Joanna Maria Wenda1, Katarzyna Drzewicka1, Patrycja Mulica1

  • 1Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Warsaw 02-106, Poland.

Genetics
|July 29, 2024
PubMed

Insights

Four Pentatricopeptide repeat (PPR) proteins in Candida albicans are crucial for mitochondrial gene expression and Complex I assembly. Their absence impairs respiration, but cells can compensate using alternative oxidase 2 (AOX2).

Area of Science:

  • Mitochondrial gene expression
  • Fungal Pathogenesis
  • RNA-binding proteins

Background:

  • Pentatricopeptide repeat (PPR) proteins regulate mitochondrial and chloroplast gene expression in eukaryotes.
  • In fungi, PPR proteins control mitochondrial genome expression post-transcriptionally.
  • Candida albicans, an opportunistic pathogen, uniquely retains mitochondrially encoded Complex I (CI) subunits and cannot lose its mitochondrial DNA (mtDNA).

Purpose of the Study:

  • To characterize the function of four PPR proteins in Candida albicans that lack homologs in Saccharomyces cerevisiae.
  • To investigate the role of these PPR proteins in the expression of mitochondrially encoded Complex I subunits.
  • To understand their impact on mitochondrial function, RNA stability, and cellular respiration.

Main Methods:

  • Gene deletion studies to create PPR protein knockout strains in C. albicans.
  • Mitochondrial protein and RNA analysis to assess gene expression and stability.
  • Assessment of Complex I assembly and activity.
  • Analysis of alternative oxidase (AOX2) expression levels.

Main Results:

  • Four C. albicans PPR proteins (CaPpr4, CaPpr11, CaPpr13, CaPpr7) localize to mitochondria and are essential for Complex I (CI) subunit expression.
  • Deletion of CaPpr4, CaPpr11, and CaPpr13 abolished CI assembly, while CaPpr7 deletion decreased CI activity.
  • CaPpr13p maintains the NAD4L-NAD5 mRNA, and other PPR proteins are involved in translation or assembly of CI subunits.
  • CaAep3p, an ortholog of ScAep3p, controls ATP8-ATP6 mRNA expression.
  • Cells lacking these PPR proteins showed increased expression of the alternative oxidase 2 (AOX2), suggesting a compensatory mechanism.

Conclusions:

  • Specific PPR proteins in C. albicans are indispensable for the expression and assembly of mitochondrially encoded Complex I subunits.
  • These proteins play critical roles in post-transcriptional regulation of the mitochondrial genome, impacting cellular respiration.
  • Upregulation of AOX2 provides a compensatory pathway for respiratory defects caused by the loss of CI function.
Keywords:
Candida albicansAOXComplex IETCPARPPR proteinsmitochondria

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