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bioRxiv · 10.1101/2021.10.08.463630

The prion and HSP104 modulate cytochrome c oxidase deficiency caused by deletion of COX12

Saini, P. K.·Dawitz, H.·Aufschnaiter, A.·Thomas, J.·Amblard, A.·Stewart, J.·Thierry-Mieg, N.·Ott, M.·Pierrel, F.
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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 {Delta}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 {Delta}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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Saini, P. K., Dawitz, H., Aufschnaiter, A., Thomas, J., Amblard, A., Stewart, J., Thierry-Mieg, N., Ott, M., Pierrel, F.. 2021-10-09. The prion and HSP104 modulate cytochrome c oxidase deficiency caused by deletion of COX12. https://doi.org/10.1101/2021.10.08.463630

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