A Dynamic Actin Cytoskeleton is Required to Prevent Constitutive VDAC-dependent MAPK Signalling and Aberrant Lipid Homeostasis

Overview

Journal iScience

Publisher Cell Press

Date 2023 Aug 28

PMID 37636069

Authors

Jack Davis

Thorsten Meyer

Martin Smolnig

Daniel G J Smethurst

Lisa Neuhaus

Jonas Heyden

Filomena Broeskamp

Elizabeth S M Edrich

Oskar Knittelfelder

Dagmar Kolb

Tobias von der Haar

Campbell W Gourlay

Patrick Rockenfeller

Affiliations

Soon will be listed here.

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 aging and attenuation of adaptive response mechanisms. Cofilin is an actin-binding protein that controls actin dynamics and has been linked to mitochondrial signaling pathways that control drug resistance and cell death. Here we show that cofilin-driven chronic depolarization of the actin cytoskeleton activates cell wall integrity mitogen-activated protein kinase (MAPK) signalling and disrupts lipid homeostasis in a voltage-dependent anion channel (VDAC)-dependent manner. Expression of the 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 signaling, lipid homeostasis, and cell health in .

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