The APC/C Activator Cdh1p Plays a Role in Mitochondrial Metabolic Remodelling in Yeast

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Feb 25

PMID 36835555

Authors

Ana Claudia Leite

Maria Barbedo

Vitor Costa

Clara Pereira

Affiliations

Soon will be listed here.

Abstract

Cdh1p is one of the two substrate adaptor proteins of the anaphase promoting complex/cyclosome (APC/C), a 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 Δ mutant, with 43 up-regulated proteins and 92 down-regulated proteins. The group of significantly up-regulated proteins included subunits of the mitochondrial respiratory chain, enzymes from the tricarboxylic acid cycle and regulators of mitochondrial organization, suggesting a metabolic remodelling towards an increase in mitochondrial respiration. In accordance, mitochondrial oxygen consumption and Cytochrome oxidase activity increased in Cdh1p-deficient cells. These effects seem to be mediated by the transcriptional activator Yap1p, a major regulator of the yeast oxidative stress response. deletion suppressed the increased Cyc1p levels and mitochondrial respiration in Δ cells. In agreement, Yap1p is transcriptionally more active in Δ cells and responsible for the higher oxidative stress tolerance of Δ mutant cells. Overall, our results unveil a new role for APC/C-Cdh1p in the regulation of the mitochondrial metabolic remodelling through Yap1p activity.

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