The [PSI + ] prion modulates cytochrome c oxidase deficiency caused by deletion of COX12

• Published in: Molecular biology of the cell 2022-12, Vol.33 (14), p.ar130-ar130
• Main Authors: Saini, Pawan Kumar, Dawitz, Hannah, Aufschnaiter, Andreas, Bondarev, Stanislav, Thomas, Jinsu, Amblard, Amélie, Stewart, James, Thierry-Mieg, Nicolas, Ott, Martin, Pierrel, Fabien
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; Cytochrome-c Oxidase Deficiency; Electron Transport Complex IV - metabolism; Heat-Shock Proteins - metabolism; Humans; Life Sciences; Peptide Termination Factors - metabolism; Prions - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 1059-1524; 1939-4586; 1939-4586
• DOI: 10.1091/mbc.E21-10-0499

Cytochrome 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 Δ 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 also increased respiration of the Δ ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [ ] 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.