The APC/C activator Cdh1p plays a role in mitochondrial metabolic remodelling in yeast

ABSTRACT: Cdh1p is one of the two substrate adaptor proteins of the anaphase promoting complex/cyclosome (APC/C), an ubiquitin ligase that regulates proteolysis during cell cycle. In this work, using a proteomic approach, we found 135 mitochondrial proteins whose abundance was significantly altered in the cdh1Δ mutant, with 43 up-regulated proteins and 92 down-regulated proteins. When considering the group of significantly up-regulated proteins, these included subunits of the mitochondrial respiratory chain, enzymes from the TCA cycle and regulators of mitochondrial organization, suggesting a metabolic remodelling towards an increase in mitochondrial respiration. In accordance, mitochondrial oxygen consumption and COX activity increased in the absence of Cdh1p. These effects seem to be mediated by the transcriptional activator Yap1p, a major regulator of the yeast oxidative stress response. YAP1 deletion suppressed the increased Cyc1p levels and mitochondrial respiration in cdh1Δ cells. In agreement, Yap1p is transcriptionally more active in cdh1Δ cells, and responsible for the cdh1Δ mutant higher oxidative stress tolerance. Overall, our results unveil a new role for APC/C-Cdh1p in the regulation of the mitochondrial metabolic remodelling trough Yap1p activity.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Hugo Osorio  

LAB HEAD: Clara Pereira

PROVIDER: PXD039879 | Pride | 2023-02-24

REPOSITORIES: Pride