Ergosterol reduction impairs mitochondrial DNA maintenance in S. cerevisiae

Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Mar;1864(3):290-303. doi: 10.1016/j.bbalip.2018.12.002. Epub 2018 Dec 12.

Abstract

Sterols are essential lipids, involved in many biological processes. In Saccharomyces cerevisiae, the enzymes of the ergosterol biosynthetic pathway (Erg proteins) are localized in different cellular compartments. With the aim of studying organelle interactions, we discovered that Erg27p resides mainly in Lipid Droplets (LDs) in respiratory competent cells, while in absence of respiration, is found mostly in the ER. The results presented in this paper demonstrate an interplay between the mitochondrial respiration and ergosterol production: on the one hand, rho° cells show lower ergosterol content when compared with wild type respiratory competent cells, on the other hand, the ergosterol biosynthetic pathway influences the mitochondrial status, since treatment with ketoconazole, which blocks the ergosterol pathway, or the absence of the ERG27 gene, induced rho° production in S. cerevisiae. The loss of mitochondrial DNA in the ∆erg27 strain is fully suppressed by exogenous addition of ergosterol. These data suggest the notion that ergosterol is essential for maintaining the mitochondrial DNA attached to the inner mitochondrial membrane.

Keywords: Ergosterol; Lipid droplets; Mitochondria; Rho° cells; S. cerevisiae; Sterols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosynthetic Pathways
  • DNA, Mitochondrial / drug effects*
  • DNA, Mitochondrial / metabolism
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Ergosterol / genetics*
  • Ergosterol / metabolism*
  • Gene Expression Regulation, Fungal / genetics
  • Ketoconazole / pharmacology
  • Lipid Droplets / metabolism
  • Mitochondria / metabolism
  • Oxidoreductases / metabolism
  • Oxidoreductases / physiology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology
  • Sterols / metabolism

Substances

  • DNA, Mitochondrial
  • Saccharomyces cerevisiae Proteins
  • Sterols
  • Oxidoreductases
  • ERG27 protein, S cerevisiae
  • Ketoconazole
  • Ergosterol