A dynamic actin cytoskeleton is required to prevent constitutive VDAC-dependent MAPK-signalling and aberrant lipid homeostasis

Davis, Jack, Meyer, Thorsten, Smolnig, Martin, Smethurst, Daniel G.J., Neuhaus, Lisa, Heyden, Jonas, Broeskamp, Filomena, Edrich, Elizabeth S.M., Knittelfelder, Oskar, Kolb, Dagmar, and others. (2023) A dynamic actin cytoskeleton is required to prevent constitutive VDAC-dependent MAPK-signalling and aberrant lipid homeostasis. iScience, 26 (9). Article Number 107539. E-ISSN 2589-0042. (doi:10.1016/j.isci.2023.107539) (KAR id:102349)

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Official URL: https://doi.org/10.1016/j.isci.2023.107539

Abstract

The dynamic nature of the actin cytoskeleton is required to coordinate many cellular processes and a loss of its plasticity has been linked to accelerated cell ageing and attenuation of adaptive response mechanisms. Cofilin is an actin-binding protein that controls actin dynamics and has been linked to mitochondrial signalling pathways that control drug resistance and cell death. Here we show that cofilin-driven chronic depolarisation of the actin cytoskeleton activates cell wall integrity MAPK-signalling and disrupts lipid homeostasis in a VDAC-dependent manner. Expression of the cof1-5 mutation, which reduces the dynamic nature of actin, triggers loss of cell wall integrity, vacuole fragmentation, disruption of lipid homeostasis, lipid droplet (LD) accumulation and the promotion of cell death. The integrity of the actin cytoskeleton is therefore essential to maintain the fidelity of MAPK signalling, lipid homeostasis and cell health in S. cerevisiae.

Item Type:	Article
DOI/Identification number:	10.1016/j.isci.2023.107539
Uncontrolled keywords:	actin; yeast; lipid homeostasis; cell death
Subjects:	Q Science
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Funders:	FWF Austrian Science Fund (https://ror.org/013tf3c58)
Depositing User:	Campbell Gourlay
Date Deposited:	05 Aug 2023 12:09 UTC
Last Modified:	09 Jan 2024 18:33 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/102349 (The current URI for this page, for reference purposes)

University of Kent Author Information

Davis, Jack.

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Gourlay, Campbell W..

Creator's ORCID:	https://orcid.org/0000-0002-2373-6788
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Rockenfeller, Patrick.

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