Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
The [PSI+] prion modulates cytochrome c oxidase deficiency caused by deletion of COX12. / Saini, Pawan Kumar; Dawitz, Hannah; Aufschnaiter, Andreas; Bondarev, Stanislav ; Thomas, Jinsu; Amblard, Amélie; Stewart, James; Thierry-Mieg, Nicolas; Ott, Martin; Pierrel, Fabien.
в: Molecular Biology of the Cell, Том 33, № 14, 01.12.2022, стр. ar130.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - The [PSI+] prion modulates cytochrome c oxidase deficiency caused by deletion of COX12
AU - Saini, Pawan Kumar
AU - Dawitz, Hannah
AU - Aufschnaiter, Andreas
AU - Bondarev, Stanislav
AU - Thomas, Jinsu
AU - Amblard, Amélie
AU - Stewart, James
AU - Thierry-Mieg, Nicolas
AU - Ott, Martin
AU - Pierrel, Fabien
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - Humans
KW - Prions/genetics
KW - Peptide Termination Factors/metabolism
KW - Saccharomyces cerevisiae Proteins/genetics
KW - Cytochrome-c Oxidase Deficiency
KW - Heat-Shock Proteins/metabolism
KW - Saccharomyces cerevisiae/metabolism
KW - Electron Transport Complex IV/metabolism
UR - https://www.mendeley.com/catalogue/922d7e3f-48f9-399c-81d0-66b335ee34e1/
UR - http://www.scopus.com/inward/record.url?scp=85142403724&partnerID=8YFLogxK
U2 - 10.1091/mbc.E21-10-0499
DO - 10.1091/mbc.E21-10-0499
M3 - Article
C2 - 36129767
VL - 33
SP - ar130
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 14
ER -
ID: 99683819