DOI

  • Pawan Kumar Saini
  • Hannah Dawitz
  • Andreas Aufschnaiter
  • Stanislav Bondarev
  • Jinsu Thomas
  • Amélie Amblard
  • James Stewart
  • Nicolas Thierry-Mieg
  • Martin Ott
  • Fabien Pierrel

Cytochrome c oxidase (CcO) is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of CcO oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here experimental evolution of a Saccharomyces cerevisiae Δcox12 strain for ∼300 generations allowed to restore the activity of CcO oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the cytosolic AAA+ disaggregase Hsp104. Deletion or overexpression of HSP104 also increased respiration of the Δcox12 ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [PSI+] prion, which forms cytosolic amyloid aggregates of the Sup35 protein. Overall, our data demonstrate that cytosolic aggregation of a prion impairs the mitochondrial metabolism of cells defective for Cox12. These findings identify a new functional connection between cytosolic proteostasis and biogenesis of the mitochondrial respiratory chain.

Original languageEnglish
Pages (from-to)ar130
JournalMolecular Biology of the Cell
Volume33
Issue number14
Early online dateSep 2022
DOIs
StatePublished - 1 Dec 2022

    Scopus subject areas

  • Medicine(all)

    Research areas

  • Humans, Prions/genetics, Peptide Termination Factors/metabolism, Saccharomyces cerevisiae Proteins/genetics, Cytochrome-c Oxidase Deficiency, Heat-Shock Proteins/metabolism, Saccharomyces cerevisiae/metabolism, Electron Transport Complex IV/metabolism

ID: 99683819