Pkh1p-Ypk1p and Pkh1p-Sch9p Pathways Are Activated by Acetic Acid to Induce a Mitochondrial-Dependent Regulated Cell Death

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2020 Apr 23

PMID 32318242

Citations 3

Authors

Antonio Rego

Filipa Mendes

Vitor Costa

Susana Rodrigues Chaves

Manuela Corte-Real

Affiliations

Soon will be listed here.

Abstract

The yeast undergoes a mitochondrial-dependent regulated cell death (RCD) exhibiting typical markers of mammalian apoptosis. We have previously shown that ceramide production contributes to RCD induced by acetic acid and is involved in mitochondrial outer membrane permeabilization and cytochrome release, especially through hydrolysis of complex sphingolipids catalyzed by Isc1p. Recently, we also showed that Sch9p regulates the translocation of Isc1p from the endoplasmic reticulum into mitochondria, perturbing sphingolipid balance and determining cell fate. In this study, we addressed the role of other signaling proteins in acetic acid-induced RCD. We found that single deletion of or , as shown for and , leads to an increase in cell survival in response to acetic acid and that Pkh1/2p-dependent phosphorylation of Ypk1p and Sch9p increases under these conditions. These results indicate that Pkh1p regulates acetic acid-induced RCD through Ypk1p and Sch9p. In addition, our results suggest that Pkh1p-Ypk1p is necessary for resistance to acetic acid-induced RCD. Moreover, double deletion of and has a drastic effect on cell survival associated with increased ROS accumulation and release of cytochrome , which is counteracted by overexpression of the PKA pathway negative regulator . Overall, our results suggest that Pkh1p-Ypk1p and Pkh1p-Sch9p pathways contribute to RCD induced by acetic acid.

Citing Articles

Regulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses.

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The Ypk1 protein kinase signaling pathway is rewired and not essential for viability in Candida albicans.

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Two Different Phospholipases C, Isc1 and Pgc1, Cooperate To Regulate Mitochondrial Function.

Balazova M, Vesela P, Babelova L, Durisova I, Kanovicova P, Zahumensky J Microbiol Spectr. 2022; 10(6):e0248922.

PMID: 36377885 PMC: 9769635. DOI: 10.1128/spectrum.02489-22.

Regulation of Cell Death Induced by Acetic Acid in Yeasts.

Chaves S, Rego A, Martins V, Santos-Pereira C, Sousa M, Corte-Real M Front Cell Dev Biol. 2021; 9:642375.

PMID: 34249904 PMC: 8264433. DOI: 10.3389/fcell.2021.642375.

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