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

Pawan Kumar Saini 1 Hannah Dawitz Andreas Aufschnaiter Jinsu Thomas 1 Amélie Amblard 1 James Stewart Nicolas Thierry-Mieg 2 Martin Ott Fabien Pierrel 1
1 TIMC-TrEE - Translational microbial Evolution and Engineering
TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
2 TIMC-BCM - Biologie Computationnelle et Modélisation
TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
Abstract : 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 Δ cox12 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 Δ cox12 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.
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https://hal.archives-ouvertes.fr/hal-03402829
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Soumis le : jeudi 4 novembre 2021 - 17:05:43
Dernière modification le : lundi 22 novembre 2021 - 15:18:01

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Dcox12 V11b.pdf
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Pawan Kumar Saini, Hannah Dawitz, Andreas Aufschnaiter, Jinsu Thomas, Amélie Amblard, et al.. The [PSI+] prion and HSP104 modulate cytochrome c oxidase deficiency caused by deletion of COX12. 2021. ⟨hal-03402829⟩

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