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The [PSI+] prion and HSP104 modulate cytochrome c oxidase deficiency caused by deletion of COX12

Lookup NU author(s): Dr Jim StewartORCiD

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Abstract

Cytochrome c oxidase is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of cytochrome c 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 cytochrome c oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the 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.

Publication metadata

Author(s): Saini PK, Dawitz H, Aufschnaiter A, Thomas J, Amblard A, Stewart JB, Thierry-Mieg N, Ott M, Pierrel F

Publication type: Article

Publication status: Published

Journal: Molecular Biology of the Cell

Year: 2022

Volume: 33

Issue: 14

Print publication date: 01/12/2022

Online publication date: 18/11/2022

Acceptance date: 13/09/2022

Date deposited: 22/11/2022

ISSN (electronic): 1939-4586

Publisher: American Society for Cell Biology

URL: https://doi.org/10.1091/mbc.E21-10-0499

DOI: 10.1091/mbc.E21-10-0499

ePrints DOI: 10.57711/qj5m-9346

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